Activity of a partially purified human BCGF on murine assays for B-cell stimulatory factors. I. BCGF II-like activity of human BCGF

To further characterize a human B-cell growth factor (BCGF) produced by phytohemagglutinin (PHA) P-stimulated peripheral blood T cells, a partially purified preparation of this material was tested in a number of murine assays for B-cell stimulatory factors (BSF). Human BCGF lacked murine BSF-1 activity as assessed via the induction of polyclonal proliferation of anti-IgM-stimulated murine B cells; however, this material consistently augmented the proliferative response of murine B cells to anti-IgM and a saturating dose of murine BSF-1. Human BCGF also induced proliferation in unstimulated murine B cells, and augmented the proliferative response of dextran sulfate activated murine B cells. Human BCGF is therefore capable of causing proliferation of unstimulated and activated murine B cells, and by these criteria closely resembles murine BCGF II. In contrast to murine BCGF II, however, human BCGF failed to stimulate proliferation or immunoglobulin (Ig) secretion by murine BCL1 B lymphoma cells. A murine analog of this human BCGF showing the same pattern of biological responses was found in concanavalin A-stimulated supernatants of the murine MB2.1 T-cell line and D9-Cl T-cell hybridoma. The active component of the human BCGF preparation was not due to contaminating PHA, interleukin 1, interleukin 2; interferon-gamma, or endotoxin. Comparison between the above human BCGF and a commonly used source of murine BCGF II, i.e., supernatant from antigen-stimulated D10.G4.1 T cells, provided information suggestive of BCGF II heterogeneity. Both human BCGF and D10.G4.1 supernatant caused proliferation of unstimulated and dextran sulfate-stimulated murine B cells; however, only the human BCGF preparation augmented the proliferative response of murine B cells to anti-IgM and a saturating dose of murine BSF-1, and only the D10.G4.1 supernatant stimulated BCL1 cell proliferation and immunoglobulin secretion. The data therefore indicate that the different assays for BCGF II used in this study respond to different factors, and suggest the existence of two BCGF II-like activities.     

Immortalization of BGDF (BCGF II)- and BCDF-producing T cells by human T cell leukemia virus (HTLV) and characterization of human BGDF (BCGF II)

Human peripheral T cells were transformed by human T cell leukemia virus (HTLV), and T cell lines producing BGDF (BCGF II) and BCDF were established. Among these cell lines, a cell line, TCL-Na1, secreted the highest level of both BGDF and BCDF, and the amount of BCDF secreted by TCL-Na1 cells was 900-fold more than that produced by PHA-stimulated T cells. Within the limits of our examination, none of the HTLV-transformed T cell lines produced IL 2 or BSF-p1 (BCGF I). BCDF produced by TCL-Na1 cells had a m.w. of 35,000 and a pI value of 5.5, being separated from BGDF, which was eluted in the fractions corresponding to m.w. of more than 60,000 and pI values of 5 to 6. BGDF induced both proliferation and IgM secretion in a mouse leukemic B cell line, BCL1, and these activities were not separated by either isoelectric focusing or gel filtration in the presence or absence of 0.1% Triton X-100, suggesting that the molecule designated BGDF exerted both growth and differentiation activities. BGDF acted on normal mouse B cells to induce proliferation as well as IgM secretion. The target cells of BGDF were in vivo activated B blast cells. BGDF acted on DXS-activated murine B cells to induce both proliferation and IgM secretion but not anti-Ig-activated B cells, indicating that BGDF and BSF-p1 were different molecules.     

Role of DNA synthesis in secretion of immunoglobulin from murine B cells stimulated by T cell derived lymphokines

We have investigated whether cell division is required for induction of Ig secretion from three types of B cells, which represent distinct activation states: normal splenic B cells, anti-Ig-treated B cells, and a monoclonal murine B cell tumor, BCL1. Polyclonal Ig secretion was stimulated in vitro by LPS or by lymphokines produced by EL-4 cells (EL-4 SN), which includes B cell growth factor II (BCGF II). LPS and EL-4 SN were mitogenic for all three cell populations and stimulated substantial IgM secretion from both B cells and anti-Ig blasts. Aphidicolin, a reversible inhibitor of DNA synthesis, abolished IgM secretion from B cells and anti-Ig blasts induced by either mitogen, indicating that Ig-secreting cells in these cultures are part of a cycling population. BCL1 tumor cells respond to BCGF II (but not to interleukin 2 or B cell stimulatory factor 1) with IgM secretion and cell division, allowing a direct assessment of the influence of BCGF II-stimulated cell division on secretion of IgM. Secretion by these cells during the first 24 hr of culture was not substantially affected by aphidicolin, but secretion at 48 or 72 hr was markedly inhibited. Culture of BCL1 cells for 48 hr with aphidicolin alone had no effect on cell viability or on subsequent responsiveness if the drug was removed, eliminating non-specific toxicity as an explanation of the drug's effect. Addition of aphidicolin during the last 24 hr of culture to either normal B cells or BCL1 cells was much less effective at inhibiting IgM secretion. These results indicate that the cells that secrete IgM in response to BCGF II also synthesize DNA when exposed to this factor. Thus, induction of high-rate Ig secretion from murine B cells by some stimuli, including BCGF II, may require at least one round of cell division.     

Regulation of the IgM and IgA anti-dextran B1355S response: synergy between IFN-gamma, BCGF II, and IL 2

T cell help is required for the induction of the humoral antibody response to dextran B1355S, a type II thymus-independent bacterial polysaccharide antigen. In the present study we have identified three B cell growth and differentiation factors that can substitute for T cells in the induction of IgM and IgA antibody responses to alpha(1,3) glucan determinants on dextran B1355S. Dextran B1355S stimulated murine B cell cultures supplemented with a combination of murine recombinant interferon-gamma (IFN-gamma) and a late-acting B cell growth and differentiation factor, BCGF II, produced both IgA and IgM anti-alpha(1,3) dextran plaque-forming cells (PFC). Interleukin 2 (IL 2) was not required for those responses. In contrast, recombinant IFN-gamma and recombinant IL 2 in combination supported the induction of IgA but not IgM anti-alpha(1,3) dextran PFC. In all cases, depletion of surface IgA-bearing B cells significantly decreased IgA but not IgM anti-dextran responses, indicating that the B cells responding to those lymphokines already were committed to IgA expression. These studies indicate that B cell growth and differentiation factors can exhibit differential effects on the induction of IgA compared with IgM responses.     

Characterization of monoclonal B cell growth factor (BCGF) produced by a human T-T hybridoma

We previously demonstrated the development of a cloned human T cell hybridoma that secretes B cell growth factor (BCGF) in the absence of demonstrable interleukin 2 or B cell differentiation factor. Sephadex gel filtration chromatography demonstrated the m.w. of this factor to be 18 to 20K. The present studies were performed to further characterize the biochemical properties of the molecule and to determine its target cell specificity. Temperature stability studies showed the monoclonal BCGF to be stable at 37 degrees C for 12 hr and at 70 degrees C for 15 min; however, most (93%) of the activity was lost after incubation at 70 degrees C for 30 min. Aliquots of hybridoma supernatant were exposed to buffer solutions with variable pH with no diminution in activity over a pH range of 4.0 to 10.0 BCGF activity was not affected by 2-mercaptoethanol, neuraminidase, or nucleic acid denaturing enzymes. In contrast, all activity was destroyed by 10 M urea, trypsin, and chymotrypsin. Chromatofocusing demonstrated the isoelectric point of BCGF to be 6.3 to 6.6. Finally, absorption experiments demonstrated that BCGF activity was absorbed by large, activated B cells. Mitogen-stimulated T cell blasts, small resting B cells, and CESS cells failed to absorb BCGF activity from the hybridoma supernatant. These and future studies with purified monoclonal human BCGF should enhance our understanding of its immunochemical properties and of its role in the immunoregulation of human B cell responses.     

Characterization of a T4+/Leu-8+ T cell clone that directly helps B cell Ig production by secreting B cell differentiation factor

A human T4+/Leu-8+ T cell clone (YA2) was established by phytohemagglutinin activation and interleukin 2 (IL 2) propagation. Functional characterization of this clone demonstrated that it provided potent help towards Ig production by pokeweed mitogen-stimulated B cells in the presence of small numbers of autologous T cells or by Staphylococcus aureus Cowan I (SAC)-activated B cells in the presence of B cell growth factor (BCGF). YA2 provided no help to resting B cells and minimal help to either unactivated B cells cultured with BCGF or SAC-activated B cells. Supernatant generated from clone YA2 by IL 2 stimulation had significant B cell differentiation activity but no BCGF or IL 2 activity. Thus, YA2 is a T4+/Leu-8+ potent direct helper only to B cells that are activated and proliferating due to its selective secretion of a differentiation factor, and not an activation and growth factor. The availability of phenotypically defined cloned populations of T cells with restricted functional helper activity related to the secretion of selected B cell tropic factors should prove useful in the dissection of the role of individual T cell subsets in the regulation of the human B cell cycle.     

Regulation of B cell maturation and differentiation. I. Suppression of pokeweed mitogen-induced B cell differentiation by tumor necrosis factor (TNF)

Growth and differentiation of B cells into Ig-secreting plasma cells is regulated by both T cells and macrophages and/or their secreted factors. Although the regulatory role of various cell-derived factors has been examined, the involvement of the macrophage-derived factor, TNF, in human B cell growth and differentiation has not yet been investigated. In the present study we examine the role of rTNF in polyclonal B cell response of human PBL induced by PWM. The addition of rTNF at the initiation of the culture resulted in the dose-dependent inhibition of the generation of both IgG and IgM PFC. Inhibition of PFC development followed the same dose response as rTNF-mediated cytotoxicity against a TNF-sensitive tumor target. The mechanism of rTNF-mediated suppression was examined in different experimental systems. Recombinant TNF did not affect the viability or proliferation of either the T cell or B cell subpopulations, suggesting that TNF does not mediate its suppressive effect by cytotoxic mechanisms. Kinetic studies in which rTNF was added at different times after initiation of culture indicated that inhibition can be observed as late as 4 days of culture and suggested that TNF acts at a late phase of the growth and differentiation pathway of B cells. In further studies we examined the cellular level of TNF-mediated suppression. The addition of rTNF to supernatants containing helper factors and enriched B cells resulted in no inhibition, suggesting that TNF does not act at the B cell level. This was confirmed by demonstrating that rTNF does not inhibit spontaneous PFC development by the CESS B cell line. The effect of TNF on T cell subpopulations was examined by using normal or irradiated T cells, which inactivate suppressor cells. Addition of rTNF to B cells combined with either T cell population suppressed both IgG and IgM PFC development, indicating that the target cell for suppression is the T helper cell but not ruling out an effect on macrophages or the T suppressor cells. Combined, the observed results demonstrate that rTNF suppresses PWM-induced B cell differentiation without affecting B cell proliferation. TNF appears to mediate the suppression by acting directly on T helper cells or else by regulating the production of factors controlling T cell activation and lymphokine secretion.     

Immunoregulation in the rat: cellular and molecular requirements for B cell responses to types 1, 2, and T-dependent antigens

The requirements for primary in vitro plaque-forming cell (PFC) development in cultures of purified rat splenic B cells have been examined. Rat B cells were directly responsive to the type 1 antigen trinitrophenyl-Brucella abortus (TNP-BA), but both T cells and adherent accessory cells were required for B cell responses to the type 2 antigen TNP-Ficoll and the T cell-dependent (TD) antigen sheep erythrocytes (SRBC). However, the cellfree supernatants from concanavalin A-induced spleen cells of rat or mouse origin replaced the requirement for T cells and macrophages, and resulted in PFC development in response to TNP-Ficoll and SRBC and augmented PFC numbers in response to TNP-BA. Culture supernatants from induced murine T cell and macrophage cell lines were used to partially deduce the molecular requirements for the support of PFC development by rat B cells to these three antigens. Supernatants from the EL-4 (EL-4 sup) and B151 K12 (B15 sup) T cell lines augmented TNP-BA responses, suggesting that B cell growth factor II (BCGF-II) mediated this effect. An admixture of purified interleukin 2 (IL 2) and B15 sup supported PFC development to SRBC; indicating that IL 2, BCGF-II, and the T cell-replacing factor in B15 sup (B15-TRF) were sufficient to support this response. In addition, the IL 2 plus B15 sup-supported anti-SRBC PFC response was increased by the addition of an interleukin 1-containing fraction from the supernatant of the macrophage line P388D1. PFC development in response to TNP-Ficoll had the most stringent requirements and only occurred in the presence of EL-4 sup and B15 sup (IL 2, BCGF-I, BCGF-II, EL-TRF, B15-TRF). These data indicate that different cellular and molecular requirements exist for PFC development in response to types 1, 2, and TD antigens by rat B cells.     

A novel role for accessory cells in T cell-dependent B cell differentiation

The monocyte requirement for pokeweed mitogen-induced T cell-dependent B cell activation was reexamined. We report a dichotomy in the requirement for accessory cells in B cell proliferation and differentiation. Adherent cell-depleted human peripheral blood mononuclear cells which contained only 5% monocytes generated sufficient T cell help for optimal B cell proliferation. However, the presence of 10 to 20% monocytes were required during the last 5 days of culture for stimulated B cells to become IgG-secreting cells. Similar numbers of monocytes were also needed for anti-CD3-induced B cell differentiation. Moreover, monocytes alone added to previously activated B cells could support B cell differentiation in the absence of T cells. To determine the role of cytokines in this system, we demonstrated that supernatants of adherent cell-depleted PBMC contained decreased IL-6 activity in comparison with unseparated PBMC, but not IL-1, IL-2, or BCGF. Recombinant IL-6, however, added back either alone or with other cytokines could not replace the effects of intact monocytes on B cell differentiation. Physical interaction between the accessory cells and the responder cells was also required. As a minimum, paraformaldehyde-fixed monocytes, IL-6, and IL-1 were needed to reconstitute maximal IgG secretion. These studies suggest that accessory cells capable of producing IL-1 and IL-6 can have direct effects on the terminal differentiation of stimulated B cells.     

A B cell growth factor-like activity is secreted by cloned, neoplastic B cells

Supernatants from synchronized clones of neoplastic B cells (BCL1) were found to contain a B cell growth factor (BCGFI)-like activity. The BCGF activity in the BCL1 supernatants (SN) could synergize with EL-4 SN in the late phases of an IL 1-dependent BCGF I assay (days 5 through 8). These SN did not contain any detectable BCGF II, IL, 1, or IL 2 activity. In contrast to EL-4-derived BCGF I, which has a m.w. of approximately 18,000, the BCL1-BCGF activity has a m.w. of approximately 4500. Because the BCGF activity in BCL1 SN fluctuates with cell cycle in synchronized cultures, this BCL1-BCGF may play an auto-stimulatory role in B cell proliferation.     

Identification and characterization of a B cell growth inhibitory factor (BIF) on BCGF-dependent B cell proliferation

The culture supernatants of Con A-activated human peripheral blood mononuclear cells (PBM) contained at least two regulatory factors upon B cell proliferation. One was B cell growth factor (BCGF), which activated antigen-stimulated B cells to proliferation and clonal expansion, and the other was its inhibitory factor, arbitrarily named B cell growth inhibitory factor (BIF). This BIF inhibited the effect of BCGF on anti-mu-stimulated B cells or the monoclonal mature B cell line (CLL-T.H.) obtained from the peripheral blood lymphocytes of B cell-type chronic lymphocytic leukemia patients, which were activated only with BCGF and without adding other proliferating stimuli (e.g., anti-mu). BIF activity was detected in the 24 hr culture supernatants of Con A-activated human PBM in FCS containing medium and also in serum-free RPMI 1640 medium. This substance with BIF activity could not be derived from FCS. Con A-induced BIF (m.w. of 80,000 and an isoelectric point of pH 5.4) was analyzed by Sephadex G-200 gel filtration and chromatofocusing. BIF was stable at pH 2.0 and at 56 degrees C for 30 min. Partially purified BIF had no effect on cell viability and almost no interferon activity (less than 1 IU/ml). BIF with high titer had a slight but significant inhibition on TCGF-dependent T cell growth and on PHA or Con A responses, but the extent of these inhibitions was far less than that of BCGF-dependent B cell growth. Absorption of BIF with Con A blasts made its inhibition on T cell growth even less. On the other hand, BIF activity could not be absorbed with Con A blasts but was almost absorbed with large numbers of CLL-T.H. cells. BIF had almost no inhibitory effect on the proliferation of a mouse fibroblast cell line (NIH 3T3), a mouse myeloma cell line (NS-1), human lymphoid cell lines (MOLT-4, HSB-2, and Daudi), or a human myeloid cell line (K-562). BIF-producing cells were estimated to be T cells and were identified as T8+ T cells. On the other hand, Con A-induced BCGF was demonstrated to be produced predominantly by T4+ T cells. These results show that human B cell proliferation is regulated by interaction between T4+ and T8+ cells via soluble factors, namely BCGF and BIF, respectively.     

Noncytotoxic functions of natural killer (NK) cells: large granular lymphocytes (LGL) produce a B cell growth factor (BCGF)

Highly purified human large granular (LGL), depleted of any detectable contaminant T and B cells or monocytes, were found to be potent producers in vitro of a soluble B cell growth factor (BCGF) able to sustain proliferation of B cells activated by anti-mu. Activation by lectins (phytohemagglutinin, PHA, concanavalin A, Con A; and pokeweed mitogen, PWM) was required to induce the production of high levels of this BCGF from cultured LGL. Production of BCGF was also detected after the binding of LGL with natural killer (NK)-sensitive (K562) but not with NK-resistant (RL male 1) target cells. In contrast to T cells, LGL did not need the additional presence of accessory cells to reach optimal production of BCGF by 72 hr of culture. The subpopulation of LGL responsible for the production of BCGF had phenotypic characteristics associated with NK cells (3G8+, HNK1+/OKT11+, DR-, OKT3-, Leu-M1-), and separated cells with these markers exerted high levels of NK activity. Selective production of BCGF also was obtained from cytotoxic clones derived from LGL. A partial characterization of the LGL-derived BCGF was performed by gel filtration. BCGF activity was detected in fractions with estimated m.w. of 20,000 and 45,000. The LGL-derived BCGF activity was resistant to reduction with 2-mercaptoethanol and was stable at -20 degrees C for months. Conversely, heating (56 degrees C for 1 hr) or digestion with trypsin greatly reduced the LGL-derived BCGF activity. These findings strongly suggest that LGL including those with NK activity can play an important positive role in the early events of the B cell-mediated immune response.     

Physicochemical and functional properties of murine B cell-derived B cell growth factor II (WEHI-231-BCGF-II)

A murine B lymphoma cell line, WEHI-231, constitutively secreted a kind of B cell stimulatory factor (BSF) that induced proliferation and IgM secretion in splenic B cells as well as BCL1 cells. Growth- and differentiation-promoting activities were not separated by various kinds of chromatographies on the basis of the m.w., isoelectric point, or hydrophobicity, and the degree of both activities in crude supernatants, DEAE-Toyopearl, TSK-3,000SWG, Mono P, and Phenyl-5PW fractions increased in a dose-dependent manner with complete correlation. The partially purified factor (WEHI-231-BGDF) did not show any other activities, such as IL 1, IL 2, interferon, or colony stimulating factor. WEHI-231-BGDF induced proliferation and IgM secretion in activated B cells with low density, but not in small resting B cells. WEHI-231-BGDF showed synergistic effect with dextran sulfate but not with anti-Ig in the induction of proliferation or IgM secretion in small resting B cells. WEHI-231-BGDF did not show any effect on Xid B cells. The relationship with several T cell-derived BSF and the significance of B cell-derived BSF in the B cell responses are discussed.     

Functional properties of two human B cell growth factor species separated by lectin affinity column

The supernatants from PHA-activated normal human T cells (conditioned medium) were fractionated by differential adsorption on Con A-Sepharose columns. The effluent contained both IL 2 activity (tested on the CTL-L2 cell line) and BCGF activity (tested on anti-mu-activated normal B-enriched cells). Absorption of such effluent on PHA-activated T cell blasts removed the IL 2 activity without affecting the BCGF activity. The eluate also displayed BCGF activity (tested on anti-mu-activated B-enriched cells) without detectable IL 2 activity. The two BCGF species isolated by this criteria synergize with semipurified IL 1 to support the anti-mu-induced proliferation of highly monocyte-depleted B cells. Both BCGF species required the presence of anti-mu Ab to support the proliferation of small B cells (at the G0 stage). However, in contrast to crude conditioned medium and to the BCGF present in the effluent, the BCGF present in the eluate was unable to induce the proliferation of unfractionated or large (at the G1 stage) B cells in the absence of anti-mu Ab. These results support the existence of two functionally different human BCGF species, differing at least in their relative sugar content and distinct from IL 2.     

Development and characterization of a human B cell line that responds to B cell growth factor but not interleukin 2

The human lymphoblastoid cell line we present here proliferated in response to a 14,000 m.w. B cell growth factor (BCGF), and not to interleukin 2 (IL 2). This cell line, designated B-A3, was established by Epstein Barr virus (EBV) transformation of Staphylococcus aureus Cowan I (SAC)-activated spleen B cells, and has been maintained in RPMI 1640 medium complemented with 15% fetal calf serum (FCS) without the addition of other exogenous growth factors. A proliferative response, as measured by [3H]thymidine uptake of B-A3 cells was significantly induced by either commercial IL 2-free human BCGF preparations, or phytohemagglutinin-stimulated mixed lymphocyte culture supernatant at all FCS concentrations used in the assay. The most marked proliferation due to BCGF, however, was observed in the absence of FCS. This BCGF-induced proliferation was not influenced by IL 2 or interferon-gamma (IFN-gamma), because both recombinant IL 2 and IFN-gamma failed to induce proliferation. The response of B-A3 cells to a specific BCGF was additionally indicated by the responsiveness of this cell line to BCGF purified by a series of chromatographic steps. The BCGF to which B-A3 cells responded had a m.w. of 14,000 and was similar to low m.w. BCGF reported from other laboratories. Surface characterization of B-A3 cells, analyzed by flow cytometry with a panel of monoclonal antibodies, demonstrated that the majority of B-A3 cells were stained positively with Leu-12, HLA-DR, and surface IgG markers, whereas staining with surface IgM, IgD markers, pan T cell markers (Leu-4 and Leu-9), and IL 2 receptor (Tac) were consistently negative. Taken together, the human lymphoblastoid cell line we present here responded specifically to a low m.w. BCGF. This cell line may be of value in the purification of BCGF to homogeneity, in studies of the interactions of BCGF with human B cells, and in the identification of the BCGF receptor.     

STAT3 regulates the growth and immunoglobulin production of BCL(1) B cell lymphoma through control of cell cycle progression

STAT3 is constitutively phosphorylated on tyrosine(705) in self-renewing, CD5(+) murine B-1 lymphocytes. Nuclear extracts from untreated primary B-1 or CD5(+) BCL(1) B lymphoma cells were found to contain immunoreactive STAT3 protein that binds to a sis-inducible element present in the promoter of the p21(waf1/cip1) tumor suppressor gene and is constitutively phosphorylated on serine(727). To determine the functional significance of constitutive STAT3 activation in B lymphoma cells, a specific STAT3 antisense oligonucleotide was developed and used to examine basal BCL(1) cell growth and IgM production. Abrogating STAT3 expression in BCL(1) cells inhibited their proliferative capacity and induced a corresponding decrease in secretion of IgM. Cell cycle analysis showed a block in progression through G1 in BCL(1) cells treated with the STAT3 antisense oligonucleotide. These results indicate that STAT3 controls cell growth and immunoglobulin secretion by enhancing progression through the G1 phase of the cell cycle in BCL(1) B cell lymphoma.     

B cell-derived BCGF functions as autocrine growth factor(s) in normal and transformed B lymphocytes

This paper demonstrates that B cell lines, as well as normal activated B cells generate and respond to B cell-specific growth factor(s) (BCGF). BCGF derived from B cells (B-BCGF) appears to be distinct from interleukin 1, interleukin 2 (IL 2), B cell stimulatory factor, BCGF-II, interferon-gamma, or transforming growth factor. It acts on activated B cells, but not on resting G0 phase B cells to induce proliferation. B cell lines, immortalized by Epstein-Barr virus, constitutively secrete 10-fold higher level of B-BCGF compared with normal activated B cells, suggesting that an activated autocrine loop might be operating in immortalized B cells. On the basis of our observations, we postulate that B cell clonal expansion may occur, at least in part, through a B-BCGF-dependent autocrine pathway similar to IL 2 effect on T cells.     

A monoclonal anti-mouse LFA-1 alpha antibody mimics the biological effects of B cell stimulatory factor-1 (BSF-1)

This study describes the generation of a monoclonal mouse x rat antibody (G-48) that recognizes a determinant on the serologically defined LFA-1 alpha-chain. It immunoprecipitates two noncovalently associated polypeptides of 176,000 and 95,000 Mr respectively from lysates of radioiodinated BCL1 cells, T cells, and B cells. G-48 mimics the biological actions of BSF-1 by inducing increased levels of Ia antigen expression on resting B cells, augmenting the proliferation of anti-delta-stimulated B cells, and in insolubilized form, inducing IgG1 secretion by LPS-activated B cells. G-48 does not have BCDF mu, BCGF II, nor IL 2 activity. These results demonstrate that LFA-1 plays an important role in B cell activation, proliferation, and differentiation.     

Identification and characterization of a B cell activation factor (BCAF) produced by a human T cell line

A human T cell line, Peer, that expresses the T cell helper phenotype produces discrete activation and growth factors for tonsillar B cells. The B cell activation factor produced by Peer is biochemically and physiologically distinct from other lymphokines known to enhance B cell proliferation, namely, interleukin 1, interleukin 2, interferon, and previously characterized B cell growth factors (BCGF). The BCGF produced by Peer is functionally similar to previously described BCGF but has a m.w. of approximately 30,000 daltons. The identification and characterization of a T cell-derived activation factor that can induce apparently resting (Go phase) B cells to enter S phase in the absence of an exogenous first signal has important implications in the additional dissection of the complex steps in the human B cell cycle.