Role of Ia.W39 in the interaction of antigen‐presenting cells with T and B lymphocytes

Abstract

Ia. W39 is a B cell differentiation antigen whose membrane expression is controlled by the xid gene. In this report we show that, analogous to its B cell expression, Ia. W39 is also present on a subset of Ia+ macrophages, indicating heterogeneity within that cell population. The Ir gene(s) for the antigenic determinants on the A chain loop of beef insulin maps to the I-Ab subregion of the H-2 complex and, as we have previously reported, is associated with the private specificity Ia. W39. Depletion of Ia. W39+ macrophages eliminates their capacity to present beef insulin to immune T cells, whereas the presentation of the multideterminant antigen trinitrophenylated ovalbumin is reduced less than 50%. Furthermore, we found that H-2b mice lacking Ia. W39+ cells are unable to make a secondary in vivo IgG plaque-forming cell (PFC) response to beef insulin, while the primary IgG PFC response is not dependent on Ia. W39. No shift in the kinetics of the response, nor development of suppressor T cells could be detected in Ia. W39- mice, which would explain their apparent nonresponsiveness to beef insulin after boosting with this antigen. These results, therefore, may reflect a difference in the Ir gene control acting at the primary vs. secondary response level.

B Cell Differentiation Antigens as Probes for Functional B Cell Subsets

“…We found that Ia.W39 has an identical tissue distribution to Lyb3; i.e., it is selectively expressed on a subset of B ceils that appears late in ontogeny. In addition, Ia.W39 is expressed on a subset of antigen presenting cells, which are mainly macrophages (Huber & Rosenwasser 1982). Thus, we found that 15-20% of highly purified macrophages from spleen and peritoneal cavity of adult, but not newborn H-2'' mice express Ia.W39, constitufing about half of the la* macrophages (30-40%).…”

“…A more conclusive experiment was carried out by depleting macropbages from a B6 responder animal of Ia.W39* cells. Tbe remaining ceils, which still contain a subset bearing conventional la antigens, were specifically depleted in their capacity to present beef insuHn to immune responder T cells, while they were still able to present multideterminant antigens (Huber & Rosenwasser 1982). These results unequivocally show that Ia.W39(a) is expressed on a subset of antigen presenting cells and (b) is essential for presentation of beef insulin to immune T cells.…”

“…W39* subset is required for presentation of beef insulin (Rosenwasser & Huber 1981). Furthermore, we found that xid defective mice are unable to mount a secondary PFC response to beef insulin, although they seem to make a normal primary IgG response (Huber & Rosenwasser 1982). Interestingly, tbe responsiveness profile of the bml2 mutant looks very similar to that of the xid defective mouse; namely, the bml2 is specifically unresponsive to beef insulin, and its macrophages are unable to present this antigen to immune B6 wildtype T cells (Lyn etal.…”

“…From our direct cytotoxicity experiments we know that la.W39 is also expressed on a subset of macrophages. Therefore, we analyzed the profile of responsiveness by the xid defective (NXB6) Fj ^ mice to a variety of antigens that are under Ir control mapping to the/-/4^ region (Rosenwasser & Huber 1981, Huber & Rosenwasser 1982. We chose as our test system a T cell proliferation assay, which depends on antigen presentation by la bearing macrophages.…”