Expression of bcl-x during mouse B cell differentiation and following activation by various stimuli.
We have studied the expression of the novel anti-apoptotic protein bcl-x during mouse B cell differentiation and activation. We find that bcl-x is expressed throughout all stages of B cell differentiation in the bone marrow, and is only down-regulated in mature (sIgD+) B cells. Immature peripheral B cells express low levels of bcl-x even in adult animals, whereas mature resting B cells do not. Mature B cells re-express the protein following activation, achieving maximal levels after 36-48 h. The highest levels of bcl-x are observed with potent mitogenic stimuli (such as anti-CD40 + anti-Ig): B cells first express bcl-x in the G1 phase of the cell cycle and contain maximal levels in S phase. In addition, B cells from CBA/N mice, which do not proliferate when stimulated with anti-Ig, anti-CD40 or both, exhibited only low levels of the protein following culture with these stimuli. To investigate the functional significance of bcl-x in activated B cells, we tested their sensitivity to apoptosis induced by the Ca2+ ATPase inhibitor thapsigargin: B cell blasts activated with anti-CD40 and anti-Ig were resistant to this agent. The available data therefore suggest that bcl-x fulfils two roles in B cells: it promotes survival of immature B cells (which lack bcl-2) and secondly, it apparently plays an additional role in protecting activated mature B cells (perhaps those in germinal centers) from apoptotic stimuli.
Choi
M S
MS
National Institute for Medical Research, London, GB.
Holmann
M
M
Atkins
C J
CJ
Klaus
G G
GG
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D014960:X Chromosome / Q000276:immunology; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein