DIFFERENTIAL SUSCEPTIBILITY TO TOLERANCE INDUCTION IN-VITRO OF SPLENIC B-CELLS FROM SEVERAL TRANSGENIC MOUSE LINES - ROLE OF B1 CELLS

Spleen cells from transgenic mice, whose rearranged Ig receptors refle ct the repertoires of B1 (CD5(+) and ''sister'' B cells) or normal B2 cells, were examined for their ability to be rendered unresponsive. By using an anti-Ig tolerance protocol that is independent of receptor s pecificity, we previously reported that peritoneal B cells, containing primarily CD5(+) and ''sister'' B cells, were not susceptible to unre sponsiveness. Herein, we show that splenic B cells from two separate t ransgenic mouse lines, each expressing a B1-type receptor, are resista nt to tolerance induction in vitro. In contrast, splenic B cells from two other transgenic mouse lines with a large representation of conven tional B cells were sensitive to anti-Ig-mediated unresponsiveness. Th is difference does not reside in the surface Ig density, cell cycle, o r activation stage of these cells, but is reflected in the initial cal cium mobilization and tyrosine phosphorylation after surface Ig cross- linking. Therefore, these results support the hypothesis that the anti genic specificity of B cell receptors may drive cells toward the B1 su bset, as suggested by Gong et al. (Gong, Y-Z., E. Rabin, and H. H. Wor tis. 1991. Int. Immunol. 3:467-476), and that B1 cell characteristics confer the ability of B cells to withstand in vitro tolerance inductio n, irrespective of their anatomical location. The possibility that thi s results from previous antigenic experience is discussed.