Fc receptor heterogeneity: immunofluorescent studies of B, T, and "third population" lymphocytes in human blood with rabbit IgG b4/anti-b4 complexes.

IgG Fc receptors on human peripheral blood lymphocytes (PBL) were characterized by immunofluorescence studies with defined rabbit IgG b4 allotype/anti-allotype complexes. Three discrete types of Fc receptor-bearing cells, totaling approximately 33% of PBL, were identified. Fc receptors of the three types differed in their sensitivity to trypsin and in either absolute or localized density (topography) as determined by variable requirements for anti-IgC cross-linking in order to visualize bound complexes microscopically. The question of additional heterogeneity related to differences in individual Fc receptor affinity for complexed IgG was not approached in this study. Ten to 15% of PBL had pronase-sensitive, trypsin-resistant Fc receptors readily detected by direct immunofluorescence by using large fluorescein-conjugated complexes prepared near equivalence. Double label and lymphocyte fractionation experiments established this population to be largely distinct from suface IgM+ B cells and T cells, and identical to EA Ripley rosette-forming cells. Approximately 50% of surface IgM+ B cells and approximately 10% of T cells had lower density Fc receptors identified by indirect immunofluorescence with small complexes prepared in antigen excess or by cross-linking fluorescein-conjugated complexes with anti-rabbit IgG anti-serum. An additional approximately 15% peripheral T and B cells had very low density Fc receptors detectable by complexing the IgG on the cell surface by sequential incubations of cells with b4 IgG and anti-b4. Fc receptors on B and T cells were sensitive to both pronase and trypsin digestion. The heterogeneity of IgG Fc receptors on different lymphocyte subpopulations as defined by these these experiments may be of relevance for further analysis of normal and abnormal immune function.     

A receptor for IgA on human T lymphocytes.

Receptors for IgA antibody-antigen complexes were demonstrated on 2 to 18% (mean 6.7%) of human peripheral blood T cells. The proportion of cells bearing detectable IgA receptors was low in freshly prepared T cells and increased in number after 18 to 24 hr of culture similar to the time course of appearance of the Tmu receptor. These T receptors were shown to be distinctly different from Fc-IgM and Fc-IgG receptors on T cells by blocking studies with purified IgA, IgG, and IgM.     

IgM complex receptors on subpopulations of murine lymphocytes.

Murine lymphocytes from spleen, lymph node, and thymus were examined for IgM complex receptors. Lymphocytes from all three organs were found to bind SRBC sensitized with IgM from various sources including: primary anti-SRBC serum, murine and rabbit anti-Escherichia coli LPS sera, and a murine IgM myeloma (MOPC 104E). Rosette formation by lymphocytes with IgM-sensitized SRBC was inhibited by soluble antigen-IgM complexes but not by IgM or antigen alone. Rosette formation was also inhibited by human IgM (Fc)5mu but not by Fab mu. Antiserum and complement treatment of the cells and subsequent recovery of the viable cells by trypsinization, filtration, and washing revealed the IgM rosette-forming cell (RFC) in the thymus to be a T cell. Spleen on the other hand was found to contain both B and T cells capable of binding IgM sensitized SRBC. Removal of both B and T cells from spleen cell suspensions eliminated all IgM RFC. The IgM complex receptor was found to be trypsin insensitive. Anti-Ig column fractionation enriched IgM RFC in spleen and lymph node suspensions passed through the columns, whereas cells bearing surface Ig, IgG complex receptors, and C3 receptors were retained in the columns.     

Receptors for IgM on rat spleen cells

Ox red blood cells (ORBCs) sensitized with rat IgM antibodies formed antibody-coated red blood cell rosettes (EAR) around 9% of rat spleen cells freshly prepared at 4 °C, while an enhancement of the rosette-forming cell (RFC) frequency to 18–20% was observed after having exposed the spleen cells to a temperature shift from 4 to 37 °C. Although the temperature shift was found to increase the RFC frequency, a shedding of IgM-Fc receptors IgM-FcR into the medium was also detected (IgM-FcR-I). Regeneration of shed receptors within 5 hr has been proved, and the sheading-regeneration cycle could be repeated several times. IgM-Fc receptors detectable after the temperature shift (IgM-FcR-II) are neither shed nor detectable on freshly prepared spleen cells. This latter type of receptor is expressed only after incubating the cells at 37 °C for an optimal period of 8–10 hr. Both type I and II IgM-FcRs were detected on T lymphocytes as well as B lymphocytes; therefore they do not mark subpopulation. Both receptors are sensitive to trypsin and the activity of both requires Ca²⁺ ions. Shed receptors are able to inhibit EAR formation by cells carrying either IgM-FcR-I or IgM-FcR-II. They are sensitive to higher temperatures and agglutinate ORBCs sensitized by IgM antibodies in the presence of Ca²⁺ ions. EAR-inhibiting capacity was detected in two fractions obtained by gel chromatography of the supernatant after shedding. The elution volume of one of the active fractions corresponds to 130,000 daltons (D), and that of the other to approximately 50,000 D.     

FcγR expressed on T-cell hybrids: Specificity,behavior and relationship with Ia antigens

The fine specificity of receptor for the Fc portion of IgG (FcγR) expressed on T-cell hybrids secreting soluble FcγR (sFcγR) which suppresses antibody production, was investigated. FcγR was found to bind IgG from mouse, human, and rabbit species. It reacted with mouse IgG1 and IgG2a but not IgG2b, and human IgG1 and IgG3 but not IgG4. Mouse IgG and their subclasses bound more avidly to FcγR than human and rabbit IgG. FcγR of T-cell hybrids was sensitive to pronase and resistant to trypsin. In kinetics experiments, the behavior of FcγR on the membrane of T-cell hybrids was analyzed and compared to that of I-region-coded antigens expressed on these hybrids. Upon incubation at 37 °C in balanced salt solution (BSS), T-cell hybrids released FcγR into the medium. The reexpression of FcγR, after pronase cleavage or shedding, was complete within 3 hr of incubation in culture medium and required protein synthesis. I-A-coded antigens, present on these hybrids, disappeared simultaneously with FcγR upon incubation of cells at 37 °C in BSS. Within 3 hr of incubation in culture medium, although the reexpression of Fc°R was complete, no Ia antigens could be detected. They were reexpressed later, as tested after 19 hr of culture. During a single growth cycle, the expression of FcγR was maximal during log phase.     

An appraisal of Fc receptors on human peripheral blood B and L lymphocytes.

Human circulating lymphocytes with easily detectable surface immunoglobulin have been divided into two populations, B cells and L cells. This second population lacks membrane-incorporated Ig, but has a receptor for membrane-labile cytophilic IgG. In this study purified B and L lymphocytes were examined for Fc receptors that bind aggregated IgG and IgG complexed to erythrocytes. Purified lymphocyte populations were prepared by nylon columns and by negative selection with rosetting techniques. L lymphocytes bound aggregated guinea pig and human IgG, and formed rosettes with human erythrocytes sensitized with Ripley IgG (EA). Treatment of L lymphocytes with trypsin had no effect on the receptors for IgG. B lymphocytes did not bind EA and attachment of aggregated IgG was variable; up to one-third of these cells fixed aggregated human IgG to the cell membrane. Trypsin treatment abolished binding of Agg-IgG to B cells in sharp contrast to its effect on L cells. Furthermore, double-label immunofluorescence studies showed that cells with both membrane-incorporated Ig and receptors for aggregated guinea pig IgG were rare. These studies indicate that human peripheral blood B lymphocytes lack a high affinity, trypsin-resistant Fc receptor that is present on L lymphocytes.     

Receptors for IgM on certain human B lymphocytes.

A receptor for IgM was demonstrated on the surface of human B lymphocytes by using a rosette technique with ox erythrocytes coated with rabbit IgM antibody (EAM). Lymphocytes forming rosettes with EAM did not bind sheep red cells, had membrane Ia-like antigens and, in some instances, surface immunoglobulin. The specificity of EAM rosettes was confirmed by inhibition experiments with purified human Ig. IgM but not IgG molecules inhibited the rosette reaction. In addition, inhibition of EAM rosettes with IgM fragments showed that the receptor has affinity for a part of the molecule located in the Fc portion. By analogy with the receptors previously found on certain human T cells, receptors for IgM were not detected on freshly isolated B cells, but were expressed after overnight culture in IgM-free media. Studies on different human lymphoid tissues showed that IgM receptors are expressed on a limited percentage of both circulating and noncirculating B cells. In addition to normal B cells, the malignant B cells of a majority of cases of chronic lymphocytic leukemia expressed the receptors for IgM.     

Comparison of phorbol ester/calcium ionophore and phytohemagglutinin-induced signaling in human T lymphocytes. Demonstration of interleukin 2-independent transferrin receptor gene expression

The proliferation of human T lymphocytes is regulated, in part, by the coordinated expression of genes encoding T cell growth factor (interleukin 2 (IL-2), IL-2 receptors, and transferrin receptors (TFR). We examined the time course of accumulation of mRNA for these genes in T cells stimulated with the phorbol ester, phorbol 12,13-dibutyrate (PDB) and the calcium ionophore, ionomycin, and compared their expression to T cells stimulated with phytohemagglutinin. In cells treated with PDB/ionomycin, maximum expression was observed at 3 hr for IL-2 mRNA and at 6 hr for TFR mRNA, whereas the level of IL-2 receptor mRNA reached a peak 24 to 48 hr after stimulation. In phytohemagglutinin-stimulated T cells IL-2 mRNA was detectable within 3 hr but peaked later at 12 hr; the level of IL-2 receptor mRNA similarly peaked 24 to 48 hr later. Accumulation of TFR mRNA in phytohemagglutinin-stimulated T cells, however, was not detectable at 6 hr and reached a peak only between 12 to 24 hr. The early accumulation of TFR mRNA in PDB/ionomycin-stimulated T cells seemed, in part, independent of the interaction of IL-2 with its own receptor, because TFR mRNA was detectable as early as 1 hr after stimulation and addition of cycloheximide before addition of PDB/ionomycin did not abolish the PDB/ionomycin-induced accumulation of TFR mRNA. In addition, either PDB or ionomycin used alone induced the expression of TFR mRNA but not IL-2 mRNA. These results indicated that the combination of PDB/ionomycin accelerated the expression of IL-2 and TFR genes in T cells compared to phytohemagglutinin and triggered an IL-2-independent pathway for the induction of TFR mRNA.     

A novel IgA receptor expressed on a murine B cell lymphoma.

The specificity and properties of a novel IgA receptor expressed on the surface of a tissue culture-adapted B cell lymphoma, T560, that originated in murine gut-associated lymphoid tissue, have been explored. Like the IgA receptors of murine T and splenic B cells studied by others, the T560 IgA receptor is trypsin sensitive and neuraminidase resistant and is up-regulated on T560 cells by exposing them overnight to high concentrations of polymeric IgA. Unlike them, the T560 IgA receptor is inhibited by low concentrations of IgM and high concentrations of IgG2a and IgG2b, binds at pH 4.0 but not at pH 8.0, is down-regulated by activation of protein kinase C and is sensitive to phosphatidylinositol-specific phospholipase C, indicating that it is glycosyl phosphatidylinositol-linked to the cell membrane. It is not a cell-bound form of galactosyl transferase, does not appear to bind to Ig through carbohydrate residues and does not react specifically with antibody to secretory component. It may be a completely new, cross-reactive receptor, perhaps related in some way to the polymeric Ig receptor or to the receptor for IgA expressed on the apical surface of Peyer's patch M cells, which is known to cross-react with IgG. Alternatively, it may be homologous to the highly IgA-specific Fc alpha R of T cells but, perhaps because of its glycosyl phosphatidylinositol linker, may have an ability to move and interact with other Ig receptors on the cell surface such that Ig bound to them are cross-inhibitory.     

Regulation of antibody release by naturally occurring anti-immunoglobulins in cultures of pokeweed mitogen-stimulated human peripheral blood lymphocytes

Immunoregulatory influences of human anti-immunoglobulins (anti-Ig) were studied in cultures of peripheral blood lymphocytes (PBL) from 11 normal donors. Pokeweed mitogen (PWM)-stimulated PBL released anti-Ig specific for Fab or Fc fragments of IgG, often within the first 24 to 72 hr in vitro. PBL that released more than 1 ng/ml IgM anti-Fab during the first 72 hr in vitro ultimately produced significantly less antibody (Ab) by the 12th day than PBL that released no detectable IgM anti-Fab during the first 3 days in culture. Adding affinity-purified human anti-Fab to PWM-stimulated PBL also suppressed the later Ab release by these cells. Suppression was polyclonal, affecting IgM anti-Fc, IgM anti-Fab, and IgM anti-tetanus toxoid Ab, and was directly dependent on the quantity of anti-Fab added. Anti-Fab Ab, isolated from single donor sera, were more suppressive, nanogram for nanogram, than were equal quantities of IgG anti-Fab obtained from Cohn Fraction II, when added to autologous donor PBL in vitro. Affinity-purified IgM anti-Fc, from pooled rheumatoid arthritis patient sera, also suppressed Ab release by PWM-stimulated PBL in a dose-dependent manner. These observations suggest that anti-Ig may exert a significant immunoregulatory role in man that can override to some extent the T cell-dependent stimulus for polyclonal B cell activation provided by PWM.     

Characterization of canine T-lymphocyte subpopulations: the detection of T mu and T gamma lymphocytes with homologous and heterologous immunoglobulins and the requirements for Fc receptor expression

Erythrocyte antibody (EA) rosette techniques employing sheep red blood cells sensitized with canine (homologous) and rabbit (heterologous) IgM and IgG antibodies were used to determine the number of cells with Fc receptors for IgM (Tμ) and IgG (Tγ) among T lymphocytes isolated from peripheral blood and lymph nodes of dogs. The percentages of Tμ and Tγ lymphocytes detected were found to be independent of the species origin of sensitizing antibody. Among peripheral blood T lymphocytes there were 53.0 ± 2.7% Tμ cells and 18.4 ± 3.6% Tγ cells. T lymphocytes obtained from lymph nodes were 62.1 ± 5.4% Tγ and 15.7 ± 2.6% Tγ. The number of Tμ cells detected increased from 20.0% when freshly isolated to 49.1 ± 4.1% after in vitro culture for 2–16 hr. The expression of the Fc-μ receptor in culture was inhibited by cycloheximide, demonstrating a requirement for active protein synthesis. In contrast, the number of Tγ lymphocytes detected did not vary between freshly isolated cells and those which had been cultured for 16 hr. Expression of the Fc-γ receptor during this time period was not inhibited by cycloheximide.     

IgM binding protein expressed by activated B cells

We have identified an IgM binding protein, a single chain polypeptide of Mr 60,000, that is expressed on the surface of B lymphocytes within 18 hr following their activation with phorbol myristate acetate. The IgM binding protein was also detected on fresh leukemic B cells from individuals with chronic lymphocytic leukemia, and the level of its expression was increased after phorbol myristate acetate activation. Resting and phorbol myristate acetate-activated T cells, monocytes, and polymorphonuclear leucocytes did not express detectable amounts of the IgM binding protein. The 60-kDa protein on activated human B cells could bind secreted IgM molecules of both mouse and human origin, as well as endogenous membrane-bound IgM molecules following their cross-linkage with anti-mu antibodies. The binding of soluble IgM molecules to the surface of activated B cells was also demonstrated by indirect immunofluorescence analysis.     

A comparative study of the effect of modification of the surface of human platelets on the receptors for aggregated immunoglobulins and for ristocentin-von Willebrand factor.

The receptors for aggregated immunoglobulin G (IgG) (an Fc receptor) and for ristocetin-von Willebrand factor on human platelets were studied by means of various modifications of the platelet surface. The expression of these receptors was measured by the agglutination of platelets to ristocetin in the presence of von Willebrand factor, which is part of the factor VIII complex, and by the binding of aggregated IgG coupled to 3H-labelled diazobenzene. Treatment of platelets with chymotrypsin, trypsin, papain and pronase which removed protein and glycoprotein from the platelet under conditions where the release reaction was inhibited caused loss of the expression of the receptor for ristocetin-von Willebrand factor and an enhancement of that for aggregated IgG. Induction of membrane changes with ADP and of the release reaction with the ionophore A23187 abolished agglutination to ristocentin-von Willebrand factor but did not alter the receptor for aggregated IgC. Possible contributions of unspecific membrane changes, produced by protease treatment of platelets, to the modification of receptor expression were eliminated by the use of formaldehyde-treated platelets. Trypsin, papain and pronase destroyed the ability of these platelets to agglutinate to ristocetin-von Willebrand factor but produced no change in the binding of aggregated IgC. Therefore, the receptor for ristocetin-von Willebrand factor is truly sensitive to proteolysis while the Fc receptor is not, but is partially masked by protease-sensitive material.     

A comparative study of the effect of modification of the surface of human platelets on the receptors for aggregated immunoglobulins and for ristocetin-von Willebrand factor

The receptors for aggregated immunoglobulin G (IgG) (an Fc receptor) and for ristocetin-von Willebrand factor on human platelets were studied by means of various modifications of the platelet surface. The expression of these receptors was measured by the agglutination of platelets to ristocetin in the presence of von Willebrand factor, which is part of the factor VIII complex, and by the binding of aggregated IgG coupled to ³H-labelled diazobenzen. Treatment of platelets with chymotrypsin, trypsin, papain and pronase which removed protein and glycoprotein from the platelet under conditions where the release reaction was inhibited caused loss of the expression of the receptor for ristocetin-von Willebrand factor and an enhancement of that for aggregated IgG. Induction of membrane changes with ADP and of the release reaction with the ionophore A23187 abolished agglutination to ristocetin-von Willebrand factor but did not alter the receptor for aggregated IgG. Possible contributions of unspecific membrane changes, produced by protease treatment of platelets, to the modification of receptor expression were eliminated by the use of formaldehyde-treated platelets. Trypsin, papain and pronase destroyed the ability of these platelets to agglutinate to ristocetin-von Willebrand factor but produced no change in the binding of aggregated IgG. Therefore, the receptor for ristocetin-von Willebrand factor is truly sensitive to proteolysis while the Fc receptor is not, but is partially masked by protease-sensitive material.     

Antigen-induced acceleration of shedding and replacement of B cell antigen receptors requires mature T cells

To determine which early and intermediate events in the response of antigen-binding B cells to a T-dependent antigen (sheep erythrocytes [SRC]) require T help, the antigen-induced changes in receptor turnover and surface IgD loss in BALB/c athymic nu/nu mice were compared with that of nu/+ littermates and +/+ BALB/c mice. Nonimmune SRC antigen-binding spleen B cells (ABC) from +/+, nu/+, and nu/nu BALB/c mice coexpressed IgM and IgD, and 85 to 95% retained receptors well when incubated for 2.5 hr in 100 micrograms/ml cycloheximide (which prevents receptor replacement). Also they were able to regain their ability to bind antigen by 18 hr after pronase treatment, but not by 2 hr. However, 5 days after in vivo immunization, 1) the proportion of ABC expressing surface IgD declined from around 90% to less than 50% in +/+ mice and nu/+ mice but not in nu/nu mice; 2) substantial recovery of antigen-binding occurred by 2 hr after pronase treatment in +/+ and nu/+ ABC but not in nu/nu ABC; and 3) when spleen cells were incubated in cycloheximide, uncompensated receptor shedding reduced +/+ and nu/+ ABC by around 80% but produced only about a 10% reduction in nu/nu ABC. Thus, although the ABC in nonimmune nu/nu mice appeared normal with respect to their surface Ig turnover and expression, they failed to undergo the normal antigen-induced loss of IgD or acceleration of surface Ig shedding and replacement, suggesting that these intermediate activation events require interaction with mature T cells. To determine whether this interaction had to occur during B cell development, during the development of the immune response, or during receptor shedding or replacement itself, cell transfer experiments were carried our wherein nu/+ T cells were transferred i.v. to nu/nu littermates 1 day before immunization with SRC. In the transfer recipients, pronase-treated day 5 ABC were then able to replace and shed their receptors at the accelerated rate, like ABC from +/+ and nu/+ mice. In contrast, the co-incubation of 5-day immune nu/+ T cells with nu/nu B cells did not alter the rate of shedding or replacement.     

Surface IgG-bearing cells retain the capacity to secrete IgM

Our previous studies indicated that a large proportion of surface IgG+-primed B cells give rise to clones secreting IgM antibodies. Due to the implications of this result relative to molecular mechanisms of class switching, it was important to document that the surface IgG had been endogenously synthesized by the surface IgG+ cells and was not present as a result of cytophilic IgG. Therefore, spleen cells from immunized mice were treated sequentially with anti-immunoglobulin and protease which removed greater than 99% of surface immunoglobulin. After overnight incubation to allow resynthesis of surface immunoglobulin, the treated cells were sorted for surface IgG-bearing cells and were transferred to carrier-primed, irradiated adoptive recipients for analysis in the splenic focus assay. It was found that the majority of antibody-secreting clones derived from these surface IgG+ B cells still synthesized IgM. These data are discussed relative to current concepts of molecular mechanisms of immunoglobulin class switching.     

The class of surface immunoglobulin on virgin and memory B lymphocytes.

The class of surface immunoglobulin receptors for antigen on B cell precursors of different classes of antibody-forming cells was determined by utilizing a technique of class-specific antigen suicide. Spleen cells are first treated with a class-specific antiserum under conditions that result in the stripping of that class from the cell surface. The cells are then permitted to bind a highly radioactive trinitrophenyl (TNP)-conjugated protein, which leads to lethal irradiation of all TNP-specific B cells except those whose TNP receptors had been removed by the class-specific stripping of surface immunoglobulin. In this way, the class of antibody-forming cells resulting from TNP stimulation of B cells with different classes of surface immunoglobulin can be examined. It was found that the virgin B cell precursors of IgM-producing cells are two types: cells bearing IgM receptors only and those bearing both IgM and IgD receptors. All virgin B cells that gave rise to IgG1 antibody-forming cells had both IgM and IgD on their surfaces, demonstrating that an antigen-dependent switch from IgM and IgD to IgG1 production is a common feature of B cell maturation. In contrast, memory B cell precursors of IgG1 antibody-forming cells had predominantly IgG1 as their surface antigen receptor. The implications of these findings on current models of B cell maturation are analyzed.     

Characterization of thymus-derived lymphocyte subsets in acute Epstein-Barr virus-induced infectious mononucleosis.

Changes in thymus-derived (T) lymphocyte subpopulation numbers were studied in patients with acute and convalescent Epstein-Barr virus (EBV)-induced infectious mononucleosis (LM). T cell subsets were characterized by the presence of Fc receptors for IgG (TG), for IgM (TM) or by the absence of either receptor (Tnon-M, non-G). We found that in acute IM, total numbers of T and B lymphocytes were elevated (p less than 0.01). Of the T lymphocyte subsets, the total number of Tnon-M, non-G lymphocytes was increased six fold compared to normal subjects (p less than 0.001) and included the majority of the atypical T lymphocytes. The number of total TG and TM lymphocytes was moderately increased (p less than 0.05). In convalescent IM patients, the number of total T cells remained slightly elevated (p less than 0.02) whereas proportions and absolute numbers of B lymphocytes and T cell subsets returned to near normal levels. Thus, acute Epstein-Barr virus-induced IM is associated with a T lymphocytosis which is composed predominantly of atypical T cells which lack detectable Fc receptors for IgG or IgM.     

Heterogeneity of human natural killer cell populations.

Natural killing (NK) in human donors was determined by the ability of peripheral blood subpopulations to lyse the myeloid target, K562, in a 2 to 4 hr ⁵¹Cr release assay. The most active cell was a non-T cell which passed through nylon columns (representing 10 to 25% of column passed cells). A second column passed cell population, with characteristics of T lymphocytes (75 to 90% of column passed cells), was also capable of mediating natural killing. Non-T cells which were retained by the nylon columns (45 to 55% of adherent cells) lacked NK activity. However, nylon adherent T cells (45 to 55% of adherent cells) were consistently active in NK assays, illustrating an important subset of NK effector cell often overlooked. Both column passed and adherent T cells were further separated according to their ability to bind IgG or IgM immune complexes, showing that those mediating NK have receptors for IgG (Tγ+) but not for IgM (Tμ+).     

Trypanosoma musculi co-express several receptors binding rodent IgM, IgE, and IgG subclasses

The present work demonstrates the expression of receptors for the Fc portion of rodent Ig by the murine parasite Trypanosoma musculi. By using a rosette assay adapted to the parasite morphology and by flow cytometry analysis, three distinct receptors were identified. A receptor binding rabbit or rat polyclonal IgG and mouse monoclonal IgG1, IgG2a, and IgG2b was found on parasites purified from the blood and the peritoneal cavity of infected mice and on parasites maintained in culture conditions. This IgG receptor was degraded by pepsin. A separate receptor, binding only mouse monoclonal IgG3 was observed on cultured parasites. A receptor binding rabbit, rat, and mouse IgM was found on cultured and peritoneal parasites, but not on blood parasites. This receptor did not bind IgG or IgA but it bound mouse and rat IgE as well as IgM. It was degraded by trypsin. IgG and IgM/IgE receptors were co-expressed on single parasites. They were not of host origin but synthesized by trypanosomes as shown by reexpression in vitro after proteolytic degradation. Their expression was variable with the development of trypanosomes both in vitro and in vivo.