Opposite effects of total lymphoid irradiation on T cell-dependent and T cell-independent antibody responses

The effect of total lymphoid irradiation (TLI) on the primary antibody response to the dinitrophenylated heterologous protein, keyhole limpet hemocyanin (DNP-KLH), in complete Freund's adjuvant (CFA), and to the trinitrophenylated polysaccharide antigen, Brucella abortus (TNP-BA), was studied in BALB/c mice. The antibody response to both antigens was diminished in comparison with nonirradiated mice when antigens were injected within 3 days after TLI. When the mice were immunized 30 days after completion of TLI the antibody response to DNP-KLH in CFA was still diminished, but the antibody response to TNP-BA was enhanced 5- to 10-fold as compared with that of control animals. The opposite effect of TLI on the two antibody responses was also observed in a syngeneic primary adoptive transfer system.     

Addition of GM-CSF to a peptide/KLH vaccine results in increased frequencies of CXCR3-expressing KLH-specific T cells

T-cell trafficking is determined by expression patterns of chemokine receptors. The chemokine receptor CXCR3 is expressed on a subpopulation of type 1 T cells and plays an important role for migration of T cells into inflamed and tumor tissues. Here, we studied the chemokine receptor expression on specific T cells generated against the neoantigen keyhole limpet hemocyanin (KLH) in patients who had been immunized in the context of a tumor peptide vaccination trial with or without the adjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF). In patients immunized in the presence of GM-CSF the fraction of CXCR3⁺ KLH-specific T cells was significantly higher than in patients immunized in the absence of GM-CSF (median 45 vs. 20%, P = 0.001). In contrast, the chemokine receptor CCR4, associated with migration to the skin was found in both cohorts on less than 10% of KLH-specific T cells. These results show that CXCR3 expression on vaccine-induced T cells can be modulated by modifying the local vaccine milieu.     

Activation of helper T cells by immune complexes.

Spleen cells from mice primed with dinitrophenylated human γ-globulin (DNP-HGG) did not mount a secondary anti-DNP response in diffusion chamber cultures upon stimulation with dinitrophenylated keyhole limpet hemocyanin (DNP-KLH). The same cells, however, responded to stimulation with DNP-KLH complexed with anti-KLH antibody of rabbit or mouse origin. There is an optimal antigen:antibody ratio at which the immune complexes (IC) must be formed for maximal activity. T cells are required for the immunogenic activity of IC, since T-cell-depleted cultures did not respond. It was found that IC made with carrier and anticarrier antibody stimulated the development of carrier-specific helper T cells in cultures of spleen cells, thymocytes, and nylon wool nonadherent spleen cells from nonimmune mice. In contrast, free carrier did not elicit helper T cells. IC made with carrier and the F(ab′)₂ fragment of anticarrier antibody were immunogenic, but those made with carrier and the Fab′ fragment of anticarrier antibody were not, suggesting that helper T-cell activation is triggered by crosslinking of antigen-specific surface receptors.     

The inhibitory effect of anti-allergic agent suplatast tosilate (IPD-1151T) on methacholine- and allergen-induced bronchoconstriction in sensitized mice. asakazu@med.showa-u.dc.jp

The influence of an anti-allergic agent, suplatast tosilate (IPD-1151T; (+/-)-[2-[4-(3-ethoxy-2-hydroxypropoxy)phenyl-carbamoyl]-ethyl] dimethylsulfonium p-toluenesulfonate) on allergic bronchoconstriction induced by allergen and methacholine (MCh) were examined in mice. BALB/c mice were sensitized by intraperitoneal injection of dinitrophenylated-keyhole limpet hemocyanin (DNP-KLH) mixed with A1(OH)3 (DNP-KLH). IPD-1151T was administered orally once a day for either 5 or 14 days in doses of 10, 30 or 100 mg/kg. Bronchoconstriction was measured 24h after the final drug administration. IPD-1151T inhibited both antigen- and MCh-mediated bronchoconstriction in actively sensitized mice. The inhibition induced was closely related to the dose and frequency of oral administration of the agent. We also examined the effect of IPD-1151T on IgE production in response to DNP-KLH immunization. IPD-1151T inhibited dose-dependently both total and specific IgE concentrations in serum prepared from mice 15 days after immunization. These results strongly indicate that IPD-1151T inhibits IgE production in vivo and results in attenuating effect on bronchoconstriction.     

Immunopotentiation by SGP and Quil A. II. Identification of responding cell populations

The adjuvants SGP (a starch-acrylamide polymer) and Quil A (purified saponin) were shown to markedly augment antibody responses to T-independent (TI) antigens, suggesting that their adjuvant effects may be at least partially mediated through B cells. The ability of both adjuvants to augment primary responses to trinitrophenyl (TNP)-Ficoll (TI-2 antigen) in athymic nude mice further suggested these adjuvants affect B cells. SGP, however, did not induce a response to the T-dependent (TD) antigen dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH) in athymic nude mice, indicating it was unable to replace the requirement for T-helper cells for responses to TD antigens. Responses to TNP-lipopolysaccharide (LPS) were augmented by SGP in CBA/N X Balb/c immune defective (xid) mice. However, SGP was unable to induce a response to TNP-Ficoll in xid mice. The SGP and Quil A augmented responses to TNP-Ficoll were completely inhibited by the mitotic inhibitor, Velban, indicating that SGP and Quil A increased the plaque-forming cell (PFC) response primarily by stimulating cell proliferation, and not by recruitment of antigen-reactive cells. The effects of the adjuvants on secondary responses were investigated using adoptive transfer experiments. SGP and A1(OH)3 both increased the induction of hapten-specific memory B cells in mice primed with DNP-KLH. SGP, Quil A, and A1(OH)3 also increased priming of carrier specific T cells. Priming of memory B cells with DNP-KLH and either A1(OH)3 or SGP was prevented when T cells were depleted with anti-lymphocyte serum (ALS) at the time of antigen priming, indicating that the augmentation of memory B-cell priming by SGP and A1(OH)3 was dependent on the presence of functional T cells. SGP and Quil A were both unable to augment memory cell induction to the TI antigen, TNP-Ficoll, even though both adjuvants markedly augmented primary IgM and IgG responses to this antigen. Based on these results, it is suggested that SGP and Quil A can mediate their adjuvant effects primarily by a direct or indirect effect on B cells although the adjuvants may also affect T cells to some extent.     

The role of B lymphocytes in cell-mediated immunity II. Delayed hypersensitivity induced by dinitrophenyl-ficoll in dinitrophenyl-keyhole limpet hemocyanin-immunized guinea pigs.

Dinitrophenyl (DNP)-Ficoll will elicit typical delayed hypersensitivity skin reactions in guinea pigs immunized with DNP-keyhole limpet hemocyanin (KLH). We observed that lymph node cells (LNC) from these animals produced the lymphokine, monocyte chemotactic factor (MNL CTX) when stimulated by DNP-Ficoll in vitro. This response was antigen and hapten specific since LNC from nonimmune guinea pigs or those immunized with nonDNP containing antigens were not stimulated by DNP-Ficoll. Lymph node cells were fractionated into T- and B-cell-enriched populations to determine the nature of the DNP-Ficoll-responsive cell. Only the B-lymphocyte-enriched population produced MNL CTX in response to DNP-Ficoll. The purity of the B-cell population was demonstrated by its failure to respond to PHA and by the fact that B cells derived from DNP-although they could no longer respond without T-cell help to the T-dependent antigen, DNP-OVA. These findings suggest that the hapten-specific response of guinea pigs to DNP-Ficoll may be a form of B-cell-mediated delayed hypersensitivity.     

Antigen-nonspecific and specific suppression of lymphokine production in desensitized guinea pigs

Doubly immunized guinea pigs may be desensitized with respect to delayed hypersensitivity reactions against both antigens (anergy) by injection of large doses of either one. This anergic response therefore has both a specific and nonspecific component. The specific component of desensitization persists longer than the nonspecific one. In the present study, we have explored the mechanism of both antigen-specific and antigen-nonspecific suppression during the later stages of desensitization. Guinea pigs immunized with two antigens, DNP-KLH and DNP-EA, were desensitized with DNP-EA. The lymph node cells obtained from the animals 1 day after desensitization were unable to produce MIF in the presence of either antigen. The cells obtained 3, 5, and 7 days after desensitization were able to generate MIF when stimulated with the non-specific antigen (DNP-KLH), but not with specific antigen (DNP-EA). It was shown that both T- and non-T-cell fractions obtained 1 day after desensitization had the capacity to antigen-nonspecifically suppress MIF production. In contrast, if the cells were obtained 3 or 5 days after desensitization, T cells could inhibit only the antigen-specific production of MIF, while non-T cells were still capable of suppressing antigen-specific and nonspecific MIF production. Interestingly, when these two populations were mixed back again, it was now only suppressive to the specific antigen-induced MIF production. This latter observation indicates that nonspecific suppressor non-T cells may themselves be regulated by suppressor T cells. Furthermore, antigen-specific suppressor T cells were shown to produce soluble factor(s) which inhibited the production of MIF.     

Relation between Delayed Skin Reactivity and Macrophage Migration Inhibition or Lymphocyte Transformation in Tuberculin-Type Hypersensitivity and Jones-Mote Hypersensitivity

Precise time-course studies on delayed skin reaction, lymphocyte transformation and macrophage migration inhibition were carried out from day 3 to 270 and from day 3 to 120, respectively, in guinea pigs immunized with bovine gamma-globulin (BGG) in complete Freund's adjuvant (CFA) and those immunized with BGG in incomplete Freund's adjuvant (IFA). a) Delayed skin reactions could be elicited for a long period of time after immunization with BGG in CFA in the presence of prominent antibody production and were accompanied by induration. b) Delayed reactions could be elicited transiently after immunization with BGG in IFA and were not accompanied by induration. c) At the peak of hypersensitivity, infiltrating cells at the reaction sites were composed largely of mononuclear cells and basophils, respectively, in the animals immunized with BGG in CFA and those immunized with BGG in IFA. d) Uptake of ³H-thymidine by lymphocytes was increased remarkably in the presence of BGG when cells were obtained at early stages after immunization by both methods. e) Macrophage migration inhibition was strongly positive in animals immunized with BGG in CFA but weakly positive in those immunized with BGG in IFA. Increased lymphocyte transformation preceded the appearance of a positive migration inhibition. f) After immunization with BGG in CFA, Jones-Mote hypersensitivity appeared to precede the development of tuberculin-type hypersensitivity.     

Effect of Nippostrongylus brasiliensis infection on anti-hapten IgE antibody response in the mouse: I. Induction of carrier specific helper cells

Inoculation of infective larvae of Nippostrongylus brasiliensis into A/J, BALB/c, and SJL mice primed intraperitoneally (ip) 3 weeks before infection with 1 μg of dinitrophenylated keyhole limpet hemocyanin (DNP-KLH) mixed with 1 mg Al(OH)₃ induced a carrier effect on anti-DNP IgE and IgG₁ antibody responses when the experimental mice were secondarily immunized with an ip injection of 1 μg of DNP-coupled N. brasiliensis extract (DNP-Nb) plus alum 2 weeks after infection. The magnitude of the hapten specific antibody response did not correlate rigidly with the number of larvae in the inoculum. Thus, a dose of 100 larvae was as effective in inducing the carrier effect as a dose of 800 larvae. Kinetic studies in A/J and BALB/c mice revealed that the anti-DNP IgE antibody response reached a maximum titer 7 days after the secondary immunization. These studies also showed that the enhanced IgE antibody response persisted for more than 40 days, while the response in all control groups terminated prior to that time. Using the adoptive transfer system, it was demonstrated that lymphoid cells obtained from the spleens or the mesenteric lymph nodes of infected mice cooperated with DNP-KLH primed cells to produce hapten specific IgE and IgG, antibodies when the challenge was made with DNP-Nb but not when it was made with 1 μg DNP-ovalbumin, clearly indicating carrier specificity. The helper activity of the cells obtained from infected mice was completely abolished or greatly reduced by the in vitro treatment with anti-θ serum and complement. The helper cells with maximum activity were present as early as 14 days after inoculation. The level of helper activity gradually decreased after 14 days. The results indicate that N. brasiliensis infection is effective in inducing carrier specific helper cells of thymic origin (T cells) in anti-DNP antibody responses. These results confirm those obtained by other investigators and add the new observation that N. brasiliensis infection elicits special helper T cells which induce an enhancement as well as a prolongation of anti-DNP IgE antibody response.     

Macrophage-mediated suppression of immune responses in Toxoplasma-infected mice. II. Both H-2-linked and -nonlinked control of induction of suppressor macrophages

The suppressive effect of Toxoplasma infection on initiation of memory cells to dinitrophenylated keyhole limpet hemocyanin (DNP-KLH) was drastically different among inbred strains of mice. C57BL/6 (B6), C57BL/10 (B10), and SJL mice showed markedly suppressed secondary anti-DNP responses when infected. In contrast, the suppression did not occur in BALB/c mice. The infected DBA/2 and C3H/He mice produced moderately suppressed responses. In B6 mice, an injection with 1 X 10(2) organisms of T. gondii induced a suppressed elicitation of the memory cells to DNP-KLH. However, in BALB/c mice, the responses were not affected even by inoculation with 1 X 10(4) organisms. The difference in the suppressive effect of infection between B6 and BALB/c mice was also observed in the primary anti-DNP antibody responses to DNP-KLH. Both H-2-linked and -nonlinked genes appeared to be responsible for the regulation of the immunosuppression, since the suppressive effect of infection in B10.D2 mice, which have the B10 background and the same H-2 haplotype as BALB/c, was weaker than that of B10 mice, but stronger than in BALB/c mice. In vitro studies using a primary anti-sheep erythrocytes (SRBC) antibody response system demonstrated that the activation of plastic-adherent suppressor cells by Toxoplasma infection, in which suppressor macrophages have been proved to be the responsible cells for the suppressive activity, was controlled by both H-2-linked and -nonlinked genes.     

Immunopotentiating effects of the adjuvants SGP and Quil A. I. Antibody responses to T-dependent and T-independent antigens

The present study was undertaken to compare the effects of two adjuvants, SGP (a starch-acrylamide polymer) and Quil A (purified saponin), with that of aluminum hydroxide (Al(OH)3) on murine primary antibody responses to T-independent (TI) and T-dependent (TD) antigens. All three adjuvants augmented the responses to the TD antigens, dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), and sheep erythrocytes (SRBC). SGP was the most potent adjuvant and increased the primary IgG response to DNP-KLH as much as 90-fold. Quil A and Al(OH)3 had comparable effects on the primary response to DNP-KLH, but Quil A was less effective than Al(OH)3 for augmenting the primary response to SRBC. Quil A and SGP both augmented the primary IgM and IgG responses to trinitrophenyl-lipopolysaccharide (TNP-LPS), TNP-Brucella (TI-1 antigens), and TNP-Ficoll (TI-2 antigens). Al(OH)3, like most commonly used adjuvants, had little or no effect on responses to TI antigens. The kinetics of the response to TNP-Ficoll was altered by SGP, since peak responses were maintained for at least 7 days, while the response to TNP-Ficoll alone peaked on Day 4 and had declined considerably by Day 7. Both SGP and Quil A could augment responses to both optimal and suboptimal doses of antigen. The adjuvant activity of SGP was diminished, but still effective, when smaller amounts of SGP were used with the immunizing antigen, and all three adjuvants were able to augment primary responses when given in separate injections from the antigen. These results demonstrate that SGP is a very effective adjuvant, and show that both Quil A and SGP have a unique ability to increase antibody responses to TI antigens, suggesting that their effects may be mediated at least partially through B cells.     

Avian delayed-type hypersensitivity: adaptation of the migration-inhibition assay

In this study White Leghorn cockerels were sensitized with Mycobacterium tuberculosis and/or bovine gammaglobulin (BGG). The migration of spleen cells from chickens with delayed dermal hypersensitivity to PPD was markedly inhibited in the presence of PPD but not by BGG. When birds were made doubly sensitive to mycobacteria and BGG, the migration of their spleen cells was inhibited by both antigens. Cells from animals immunized to produce high levels of circulating antibody to BGG were not inhibited in the presence of antigen. Sensitive spleen cells incubated with specific antigen elaborated a substance into the medium which inhibited the migration of normal cells. The results of these experiments indicate that the delayed hypersensitive response in birds parallels that of the mammal in that it is antigen specific, reproducible, independent of the antibody response, and transferable to normal cells with a soluble cell-free product.     

Ontogeny of the immune system in Xenopus: II. Antibody repertoire differences between larvae and adults

The larvae and adults of genetically identical clones of Xenopus each produce different populations of antibodies to dinitrophenylated keyhole-limpet hemocyanin (DNP-KLH) upon immunization. The larvae and adults differed with regard to the affinity of their IgM antibodies and the isoelectric-focusing pattern of their low-molecular-weight-Ig (IgG equivalent) antibodies. The larval antibody repertoire for DNP was not changed by the addition of adult helper T cells. Thus, the expression of a larval repertoire is the result of a B-cell pool peculiar to larvae and is not influenced, except in its quantity, by adult T cells.     

Augmentation of the antibody response by antigen-specific glycosylation-enhancing factor

BDF1 mice were immunized with a protein antigen, such as ovalbumin (OA) or keyhole limpet hemocyanin (KLH), absorbed to aluminum hydroxide gel, and their spleen cells were stimulated by homologous antigen for the formation of glycosylation-enhancing factor (GEF). It was found that GEF obtained from OA-primed spleen cells had affinity for OA, whereas those derived from KLH-primed spleen cells had affinity for KLH. Nonspecific GEF, which was obtained by stimulation of normal spleen cells with pertussis toxin, failed to bind OA or KLH. Both antigen-specific GEF and nonspecific GEF are inactivated by phenylmethylsulfonyl fluoride, but not by N-alpha-p-tosyl-L-lysyl-chloromethyl ketone. Both factors can be partially purified by binding to p-aminobenzamidine agarose and elution with benzamidine. These findings suggest that not only non-specific GEF but also antigen-specific GEF are serine protease(s). The antigen-specific GEF consisted of two m.w. species, of 65 to 85 kilodaltons (Kd) and 40 to 55 Kd, whereas nonspecific GEF consisted of 50 to 70 Kd and 20 to 30 Kd molecules. The OA-specific GEF augmented the in vitro secondary indirect PFC response of DNP-OA-primed cells to the homologous antigen, but failed to affect the PFC response of DNP-KLH-primed cells to DNP-KLH. Similarly, KLH-specific GEF enhanced the response of DNP-KLH-primed cells but not the response of DNP-OA-primed cells. However, OA-specific GEF failed to replace the requirement for antigen-primed helper T cells. Antigen-specific GEF bound to alloantibodies reactive to the products of the I region of the major histocompatibility complex. The results collectively suggest that antigen-specific GEF is identical to antigen-specific augmenting factors described by other investigators.     

Chronic permeability of the central nervous system to mononuclear cells in experimental allergic encephalomyelitis in the Lewis rat.

In order to assess whether experimental allergic encephalomyelitis (EAE), a putative animal model for multiple sclerosis (MS), is an ongoing chronic disorder, we have studied the permeability of spinal cords of Lewis rats with EAE to 3H-uridine- or 3H-thymidine-labeled lymphoid cells obtained from thymuses of naive donors or from draining lymph nodes of donors injected with guinea pig spinal cord + complete Fruend's adjuvant (CFA), guinea pig myelin basic protein + CFA, or with CFA alone. During the acute clinical phase of EAE there is a high-level infiltration of 3H-thymidine- or 3H-uridine-labeled cells into the spinal cords. After clinical recovery from EAE up to 58 days post-inoculation, there is a low-level infiltration of 3H-thymidine-labeled cells into the spinal cords. A similar infiltration into the spinal cords by 3H-uridine-labeled cells was not detected. Donor cells from animals immunized with CFA alone showed similar levels of infiltration into the spinal cords of animals with EAE as donor cells from animals immunized with the encephalitogenic emulsion. Spinal cords from recipients immunized with CFA alone showed no increased permeability to labeled cells. Heat-killed labeled cells did not migrate into the spinal cords of animals with EAE. We conclude that a) EAE is a chronic disease and in this regard is a valid model for MS; and B) in the chronic phase of EAE, recently divided cells (3H-thymidine-labeled cells) show higher levels of migration into the target tissue than 3H-uridine-labeled cells.     

The role of cytoplasmic free calcium concentration in B-cell tolerance

Calcium is an important factor in the immune response. Extracellular calcium is required for antibody production by B lymphocytes. Several investigators have demonstrated that crosslinking of receptors on B lymphocytes by anti-mu antibody induces an increase in intracellular calcium. There are few data on the role of intracellular calcium mobilization or calcium influx in tolerance induction in B cells. We studied changes in free intracellular calcium concentration ([Ca+2]i) induced by exposure of dinitrophenyl (DNP)-specific B cells to the tolerance-inducing conjugate DNP-murine IgG2a (DNP-MGG). Splenic B cells enriched for DNP-specific cells and DNP-specific continuous B-cell lines were used for the studies. Exposure of B cells to the tolerogen DNP-MGG, the antigen DNP-keyhole limpet hemocyanin (DNP-KLH), or the antigen DNP-Ficoll induced an increase in free [Ca+2]i which was due to both mobilization of Ca+2 from endoplasmic reticulum (ER) and influx of extracellular Ca+2. This increase was DNP specific since no significant change was seen with carriers alone and no change was seen in cells that were not DNP specific. The DNP-MGG and DNP-Ficoll induced the same amount of Ca+2 release from ER but the release induced by DNP-KLH was higher. When B cells, which were made tolerant by in vitro incubation with DNP-MGG, were incubated with antigens, a mobilization of Ca+2 from endoplasmic reticulum occurred that was the same as that of nontolerant B cells. Since Ca+2 mobilization is associated with Ig receptor-dependent early B-cell activation, it is likely that the tolerant B cell can still receive an activation signal through the Ig receptors.     

Antibody repertoire development in fetal and neonatal piglets. VIII. Colonization is required for newborn piglets to make serum antibodies to T-dependent and type 2 T-independent antigens

Cesarean-derived piglets were reared for 5 wk under germfree conditions or monoassociated with a benign Escherichia coli (G58-1) or a enterohemorrhagic strain (933D) derived from O157:H7, and immunized i.p. with the T-dependent (TD) Ags fluorescein-labeled (FL) keyhole limpet hemocyanin or trinitrophenylated (TNP) keyhole limpet hemocyanin and the type 2 T-independent Ags TNP-Ficoll or FL-Ficoll. Only colonized piglets showed an increase in serum IgG, IgA, and IgM and had serum Abs to FL, TNP, and colonizing bacteria. While serum Abs to FL or TNP appeared following colonization alone, secondary responses were restricted to piglets immunized using TD carriers. While animals colonized with 933D had significantly higher total serum IgG and IgM levels and specific IgG Abs than those colonized with G58-1, no differences were seen in serum IgA levels, B cell diversification in the ileal Peyer's patches, and specific activity (ELISA activity per micrograms of Ig) of pre-boost serum IgG and IgM anti-TNP and anti-FL Abs. Serum IgA Abs to TNP, FL, or bacteria were not detected. Ag-driven responses, as measured by an increase in specific Ab activity, were only observed in secondary responses to TD Ags and to colonizing, pathogenic E. coli. We propose that germline-encoded, isotype-switched B cells in newborn piglets differentiate to Ab-secreting cells 1) after stimulation by bacteria-activated APCs or 2) through direct stimulation by bacterial products. We further propose that Ag-driven systemic responses require both bacterial colonization and TD Ags translocated to the peritoneum.     

In vitro studies on transplantation immunity. II. The migration inhibition in homograft reactions in guinea pigs

The migration of peritoneal exudate cells from guinea pigs exhibiting transplantation immunity is inhibited in the presence of donor antigens. This inhibition of migration is demonstrable whether the donor transplantation antigens are presented in the form of viable cells (peritoneal exudate cells) or as particulate subcellular antigens (spleen microsomes). A greater degree of inhibition was observed when transplantation immunity was induced with lymphoid cells in Freud's adjuvant compared to sensitization with orthotopic skin grafts. There was no inhibition of migration in mixtures of normal allogeneic cells or when peritoneal cells from guinea pigs exhibiting tuberculin hypersensitivity were mixed with similar cells from normal animals. Finally, supernatants from cultures of sensitive lymphocytes plus donor antigens inhibited the migration of normal peritoneal cells indicating the presence of migration inhibitory factor (MIF) activity.     

Numbers and avidity of anti-DNP antibody plaques in different inbred mouse strains

Spleen cells of mice from eight inbred strains and three F₁ hybrids, undergoing a secondary immune response to dinitrophenylated keyhole limpet hemocyanin (DNP-KLH), were examined for numbers of indirect DNP-specific plaque forming cells (PFC) as well as avidity of anti-DNP antibodies. The results indicated that the magnitude of the immune response is under genetic control. Differences in average avidity and heterogeneity of avidity were found among different mouse strains, suggesting genetic control of these parameters. However, no simple pattern of inheritance for these characteristics emerged from the study.     

Ontogeny of the immune system in Xenopus

Abstract. The larvae and adults of genetically identical clones of Xenopus each produce different populations of antibodies to dinitrophenylated keyhole-limpet hemocyanin (DNP-KLH) upon immunization. The larvae and adults differed with regard to the affinity of their IgM antibodies and the isoelectric-focusing pattern of their low-molecular-weight-Ig (IgG equivalent) antibodies. The larval antibody repertoire for DNP was not changed by the addition of adult helper T cells. Thus, the expression of a larval repertoire is the result of a B-cell pool peculiar to larvae and is not influenced, except in its quantity, by adult T cells.