ANTIGEN-DEPENDENT SELECTION OF B-LYMPHOMA CELLS VARYING IN IA DENSITY BY CLONED ANTIGEN-SPECIFIC L3T4A + T-CELLS - A POSSIBLE INVITRO MODEL FOR B-CELL ADAPTIVE DIFFERENTIATION

  • 1 January 1984
    • journal article
    • research article
    • Vol. 1  (4) , 253-265
Abstract
The study of Ia glycoprotein antigens has focused on the following 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, 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 was used. 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. B lymphoma [mouse] 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 preexisting 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 nonspecific 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. B cell Ia antigen expression probably is quite stable; in F1 B cells, the expression of the 2 alleles is probably independently regulated. Thus, they may account for the phenomenon of B cell adaptive differentiation on the basis of differential expression of Ia antigens on F1 B cells. they may also illustrate the mechanism by which recently reported Ia restricted, antigen-specific suppressor T cells mediate their effects. Finally, they demonstrate that Ia antigen density is a critical determinant of antigen-specific T-B interactions. Therefore, variation in Ia antigen density on individual Ia antigen bearing cells may play a critical role in determining the outcome of various immunological responses.

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