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Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM¹

Kerstin Kiefer^2,*,, Pamela B. Nakajima^2,*, Jennifer Oshinsky^*, Steven H. Seeholzer^*, Marko Radic, Gayle C. Bosma^* and Melvin J. Bosma^3,*

^* Fox Chase Cancer Center, Philadelphia, PA 19111; Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107; and University of Tennessee, College of Medicine, Department of Molecular Sciences, Memphis, TN 38163

In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM^–/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM^–/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgM^low transitional splenic B cells of wild-type mice.

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 by National Institutes of Health Grants CA06927 and CA04946 and an appropriation from the Commonwealth of Pennsylvania.

² K.K. and P.B.N. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Melvin J. Bosma, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. E-mail address: MJ_Bosma{at}fccc.edu

⁴ Abreviations used in this paper: BM, bone marrow; tg, transgene; HEL, hen egg lysosome; sHEL, soluble hen egg lysozyme; sIgM, surface IgM; wt, wild type; FL, fluorescein; LM-PCR, ligation-mediated PCR; RS, recombining sequence; β₂m, β₂-microglobulin; RT, reverse transcriptase; SPL, spleen; IRS1, intronic recombining sequence 1.