Role of bcl-2 and IL-5 in the regulation of anti-IgM-induced growth arrest and apoptosis in immature B cell lines. A cooperative regulation model for B cell clonal deletion.
Recent studies of transgenic mice have confirmed that clonal deletion is involved in the development of B cells. However, little is known about intercellular and intracellular molecular events regulating B cell clonal deletion. We investigated the role of bcl-2 and cytokines in the regulation of B cell clonal deletion using anti-IgM-induced growth arrest and apoptosis in immature B cell lines as a model. We show here that overexpression of Bcl-2 protein in stably transfected immature B cells partially inhibits anti-Ig M-induced apoptosis but does not affect growth arrest. Similarly, IL-5 has a strong inhibitory effect on anti-IgM-mediated apoptosis but has a weak inhibitory effect on growth arrest. Finally, although both bcl-2 overexpression and exogenous IL-5 cooperate with bacterial LPS to block apoptosis, bcl-2 overexpression and exogenous IL-5 have no additive inhibitory effect on anti-Ig induced apoptosis. These findings indicate that anti-IgM-induced apoptosis is independently regulated from growth arrest and is controlled by at least two independent pathways: One is regulated by either Bcl-2 protein or IL-5 and the other is regulated by LPS. Activation of both the bcl-2/IL-5 and LPS pathways is necessary for complete inhibition of apoptosis, and presumably, clonal selection of the immature B cells.
Kamesaki
H
H
Department of Pathology, Georgetown University, Washington, DC 20007.
Zwiebel
J A
JA
Reed
J C
JC
Cossman
J
J
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle; D002460:Cell Line; D017637:Clonal Deletion; D004357:Drug Synergism; D015870:Gene Expression; D007075:Immunoglobulin M / Q000502:physiology*; D015848:Interleukin-5 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D019061:src-Family Kinases
D007075:Immunoglobulin M; D015848:Interleukin-5; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; C082599:protein-tyrosine kinase p55(blk); D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases