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Transitional B Cells Lose Their Ability to Receptor Edit but Retain Their Potential for Positive and Negative Selection¹

Hongsheng Wang^2,*, Jianxun Feng^*, Chen-Feng Qi^*, Zhaoyang Li^*, Herbert C. Morse, III^* and Stephen H. Clarke^2,

^* Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852; and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599

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_H12V1A Ig transgenic mice to stimulation with an anti-Igβ Ab. Our results demonstrated that immature B cells stimulated with a low concentration of anti-Igβ Ab, mimicking Ag stimulation, underwent receptor editing both in vivo and in vitro, as evidenced by the detection of dsDNA breaks at J 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-Igβ 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institutes of Health Grants AI29576 and AI43587 (to S.H.C.)

² Address correspondence and reprint requests to Dr. Hongsheng Wang, Twinbrook 1, Room 1518, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Rockville, MD 20852 and Dr. Stephen H. Clarke, Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599. E-mail addresses: wanghongs{at}niaid.nih.gov and shl{at}med.unc.edu

³ Abbreviations used in this paper: BM, bone marrow; BCR, B cell receptor; RSS, recombination signal sequence; FO, follicular; MZ, marginal zone; Tg, transgenic; ChIP, chromatin immunoprecipitation; PtC, phosphatidyl choline; DSB, dsDNA break; P.I., PMA plus ionomycin; LM, ligation mediated; int, intermediate; K4, lysine4; MSK2, mitogen- and stress-activated kinase 2.

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