Transitional B cells lose their ability to receptor edit but retain their potential for positive and negative selection.
Ligation of B cell receptors on immature bone marrow B cells, either by an endogenous Ag or by an anti-B cell receptor Ab induces secondary V(D)J gene rearrangements, termed receptor editing. Whether the same signal induces receptor editing in transitional B cells is not clear. In this study, we examined the responses of immature and transitional B cells from V(H)12Vkappa1A Ig transgenic mice to stimulation with an anti-Igbeta Ab. Our results demonstrated that immature B cells stimulated with a low concentration of anti-Igbeta Ab, mimicking Ag stimulation, underwent receptor editing both in vivo and in vitro, as evidenced by the detection of dsDNA breaks at Jkappa recombination signal sequences, whereas transitional B cells did not. The lack of dsDNA breaks in transitional B cells contrasts with their increased expression of RAG1 and RAG2, suggesting a novel mechanism that may prevent rearrangements. Furthermore, treatment of transitional B cells with high concentrations of anti-Igbeta Abs induced apoptosis, whereas low concentrations induced differentiation. Our results support the idea that transitional B cells lose the capacity to edit, but are sensitive to positive and negative selection.
Wang
Hongsheng
H
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. wanghongs@niaid.nih.gov
Feng
Jianxun
J
Qi
Chen-Feng
CF
Li
Zhaoyang
Z
Morse
Herbert C
HC
Clarke
Stephen H
SH
D000107:Acetylation; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000937:Antigen-Antibody Reactions; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006657:Histones / Q000276:immunology; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008239:Lysine / Q000276:immunology; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000187:drug effects / Q000276:immunology*; D012680:Sensitivity and Specificity
D000906:Antibodies; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D007143:Immunoglobulin Heavy Chains; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D008239:Lysine