Rescue of ileal Peyer's patch B cells from apoptosis is associated with the induction of Bcl-2 expression.
The major site of B-cell genesis in the sheep is the ileal Peyer's patch (PP). The B cells in the ileal PP undergo both extensive proliferation and massive death in association with an ongoing diversification of the immunoglobulin repertoire by somatic hypermutation. Most, if not all, the B-cell death in the ileal PP is due to apoptosis. When placed in culture, ileal PP B cells undergo rapid apoptosis. Here, we investigated the expression of the proto-oncogene bcl-2 in ileal PP cells in situ and in culture. Bcl-2 expression has been correlated with the prevention of apoptosis in many cell types. Western blotting, using anti-Bcl-2 monoclonal antibodies, revealed that a Bcl-2-reactive protein of 26,000 MW was expressed in ileal mesenteric lymph node cells, splenocytes and thymocytes from sheep, but was barely detectable in ileal PP B cells in situ or in culture. However, Bcl-2 expression could be markedly induced in ileal PP B cells cultured with phorbol ester and Ca2+ ionophore, a procedure that is known to rescue these cells from apoptosis. We hypothesize that those few B cells that survive a selection event in the ileal PP may begin to express elevated levels of Bcl-2 as they escape from the apoptotic pathway.
Motyka
B
B
Department of Medical Physiology, University of Calgary, Alberta, Canada.
Reynolds
J D
JD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D007082:Ileum / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D010581:Peyer's Patches / Q000276:immunology* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012756:Sheep / Q000276:immunology*; D013154:Spleen / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin