Polyclonal B-cell activation by a B-cell differentiation factor B151-TRF2. IV. B151-TRF2-responsive F1 B cells consist of two separate populations capable of recognizing only one of the parental I-A products expressed on B cells.

Abstract

Polyclonal IgM PFC responses of unstimulated B cells induced by a B cell differentiation factor, B151-TRF2, have been shown to involve an Ia-dependent process which is inhibitable by anti-Ia monoclonal antibody (mAb). Moreover, we have demonstrated that when T cell-depleted (B10 x B10.BR)F1 (H-2b/k) spleen cells are fractionated based on their ability to bind to a B10 (H-2b) monolayer, the B151-TRF2 responses of the adherent and nonadherent cell fractions are markedly inhibited by anti-I-Ab and anti-I-Ak mAbs, respectively. From these results, we hypothesized that B cell-recognition of self-I-A products expressed on B cells is involved in the B151-TRF2-induced polyclonal B cell activation. The present study examined the genetic and cellular requirements for the successful separation of F1 B cells with parental monolayers in order to prove recognition by B cells of self-I-A products expressed on B cells. The experiments utilizing monolayers from H-2 congenic strains revealed that identity at the I-A subregion of the H-2 complex between responding F1 B cells and monolayer cells was necessary and sufficient for the successful separation of F1 B cells. In support of this conclusion, purified B cells and B cell lines expressing only parental I-A products on the surface could function effectively as monolayers. Masking of I-A determinants expressed on the monolayer with anti-I-A mAb almost completely abolished the successful separation of F1 B cells, whereas pretreatment of Ia antigens on responding F1 B cells with anti-Ia mAbs did not affect the subsequent separation, indicating involvement of receptor-I-A product interaction rather than like-like interaction in the separation of F1 B cells by the monolayer. The B151-TRF2 responses of purified B cells obtained from athymic nude mice were specifically inhibited by the relevant anti-I-A mAb but not by anti-L3T4 and anti-LFA-1 mAbs, both of which were inhibitory to the Ia-restricted T cell responses. In addition, anti-Thy1.2 mAb plus complement-treated spleen cells from athymic F1 nude mice were successfully fractionated with parental monolayer into two separate populations with restriction specificity for only one of parental I-A products. These results negate the involvement of Ia-restricted T cells in the Ia-dependent process of the B cell activation. Finally, it was demonstrated that there was no apparent difference in the expression of respective parental I-A products between F1 B cell subpopulations adherent and nonadherent to parental monolayers.(ABSTRACT TRUNCATED AT 400 WORDS)