Physiological cell death in B lymphocytes: I. 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. Cross-linking of slg 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 slg 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 I-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 Th2 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, [3H]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 Th1-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 slg engagement. We discuss the implications of these findings for our understanding of PCD in B cells.
Gottschalk
A R
AR
Department of Pathology, University of Chicago, IL 60637.
McShan
C L
CL
Merino
R
R
Nuñez
G
G
Quintáns
J
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology* / Q000648:ultrastructure; D002453:Cell Cycle; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival; D007136:Immunoglobulins / Q000502:physiology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured
D007136:Immunoglobulins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2