Constitutive Bcl-2 expression during immunoglobulin heavy chain-promoted B cell differentiation expands novel precursor B cells.
To test for effects on B cell differentiation, we introduced immunoglobulin mu heavy chain (HC) and Bcl-2 transgenes, separately or together, into recombination-activating gene 2 (RAG-2)-deficient mice. Transgenic Bcl-2 expression led to increased numbers of RAG-deficient pro-B cells, but did not promote their further differentiation. Expression of the mu HC transgene promoted the differentiation of RAG-deficient pro-B cells into pre-B cells that also expressed certain differentiation markers characteristic of even more mature B cell stages. However, the extent of the mu HC-dependent differentiation effects was greatly enhanced by coexpression of the transgenic Bcl-2 gene, and a subset of pre-B cells from both HC and HC, Bcl-2-transgenic RAG-2-deficient animals expressed surface mu HCs that were functional as judged by cross-linking experiments. These experiments demonstrate that the pro-B to pre-B transition in vivo cannot be effected by the expression of Bcl-2 alone, and that nontransformed immature B-lineage cells are competent to receive signals through a surface mu complex.
Young
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Howard Hughes Medical Institute and the Department of Genetics and Pediatrics, The Children's Hospital, Boston, Massachusetts 02115, USA.
Mizoguchi
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Bhan
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AK
Alt
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FW
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D019254:Genes, bcl-2; D006410:Hematopoiesis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000502:physiology; D037102:Lectins; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D011506:Proteins / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011951:Receptors, Complement / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis; D051918:Sialic Acid Binding Ig-like Lectin 2; D013154:Spleen / Q000166:cytology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains; D037102:Lectins; D011506:Proteins; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017455:Receptors, IgE; D051918:Sialic Acid Binding Ig-like Lectin 2; C064655:V(D)J recombination activating protein 2; D017493:Leukocyte Common Antigens