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Antigen-dependent selection of B lymphoma cells varying in Ia density by cloned antigen-specific L3T4a+ T cells: a possible in vitro model for B cell adaptive differentiation.

The study of Ia glycoprotein antigens has focused on qualitative differences: allelic polymorphism, mutants and differences between the I-A and I-E molecules. However, as the only known function of Ia glycoproteins is in the presentation of antigen to syngeneic T cells, quantitative rather than qualitative variation might be expected to be the critical variable in cell interactions. To examine the role of Ia antigen density in T-B interactions, we have used a novel system involving the lysis of B lymphoma cells in the presence of protein antigen and cloned, antigen plus Ia specific helper T cells. The B lymphoma cells that survive this interaction can be recovered, and both their level of Ia antigen and their susceptibility to antigen-specific lysis determined. We have found that B lymphoma cells surviving lysis express less cell surface Ia antigen than the parent B lymphoma line, and are correspondingly more difficult to lyse. Several properties of this system are of interest. First, Ia antigens the genes for which are on the same chromosome as that recognized by the selecting cloned T cell are expressed at quantitatively similar levels, while those on a polymorphic homologous chromosome are not. Thus, in hybrid B cells. Ia antigen expression is regulated in cis and not trans. Second, alteration in Ia antigen expression is stable in continuous culture. Third, the variants pre-exist in the population of B lymphoma cells. Thus, the role of the T cell is to select pre-existing variants, not to generate variation. Fourth, the amount of protein antigen required to get lysis of the variant and parent lines to equivalent levels is reciprocally related to the mean cell surface density of the Ia antigen recognized by the test clone, suggesting that antigen and Ia molecules form complexes, and that complex formation is governed by the law of mass action. And finally, since the lytic cloned cells appear to effect lysis by release of a non-specific lytic intermediate, while the effect on the B cells appears to be cognate, these data are consistent with others suggesting that all T-B interactions require T cell recognition of antigen-Ia complexes at the B cell surface, but are mediated by release of nonspecific T cell factors. These results suggest that B cell Ia antigen expression is quite stable, and that in F1 B cells, the expression of the two alleles is independently regulated.(ABSTRACT TRUNCATED AT 400 WORDS)