PHYSIOLOGICAL CELL-DEATH IN B LYMPHOCYTES .1. DIFFERENTIAL SUSCEPTIBILITY OF WEHI-231 SUBLINES TO ANTI-IG INDUCED PHYSIOLOGICAL CELL-DEATH AND LACK OF CORRELATION WITH BCL-2 EXPRESSION

WEHI-231 is a murine lymphoma generally considered to represent an immature B cell. Crosslinking of sig on WEHI-231 leads to growth arrest and eventually physiological cell death (PCD). We characterized three sublines of WEHI-231 by flow cytometry and compared their responses with sig cross-linking. All sublines had identical expression of a series of common B cell surface markers (IgM, IgD, Fc gamma R, ICAM-1, and CD45), but one was l-A(-). Despite the phenotypic similarities between these sublines, anti-IgM caused aptotosis in only two sublines, although it inhibited growth in all three. The growth arrest induced by anti-IgM was reversible by lipopolysaccharide and T(h)2 clones and independent of FC gamma R engagement. Anti-IgD, unlike anti-IgM, induced neither growth arrest nor apoptosis. To further compare the sublines' susceptibility to PCD, we investigated their responses to anti-IgM by ultrastructural morphology, [H-3]thymidine release, propidium iodide exclusion, and incorporation into DNA. By all these experimental criteria, two of the WEHI-231 sublines were susceptible to PCD while the third demonstrated remarkable resistance to anti-IgM, but not irradiation or T(h)1-induced PCD. This differential susceptibility to PCD did not correlate with either bcl-2 levels in the resting cells or to the decrease in bcl-2 expression following sig engagement. We discuss the implications of these findings for our understanding of PCD in B cells.