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Two Distinct Populations of H Chain-Edited B Cells Show Differential Surrogate L Chain Dependence¹

Pamela B. Nakajima^*, Kerstin Kiefer^*,, Amy Price^*,, Gayle C. Bosma^* and Melvin J. Bosma^2,*

^* Fox Chase Cancer Center, Philadelphia, PA 19111; and Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107

Developing autoreactive B cells may edit (change) their specificity by secondary H or L chain gene rearrangement. Recently, using mice hemizygous for a site-directed VDJH and VJ transgene (tg) encoding an autoreactive Ab, we reported ongoing L chain editing not only in bone marrow cells with a pre-B/immature B cell phenotype but also in immature/transitional splenic B cells. Using the same transgenic model, we report here that editing at the H chain locus appears to occur exclusively in bone marrow cells with a pro-B phenotype. H chain editing is shown to involve VH replacement at the tg allele or VH rearrangement at the wild-type (wt) allele when the tg is inactivated by nonproductive VH replacement. VH replacement/rearrangement at the tg/wt alleles was found to entail diverse usage of VH genes. Whereas the development of edited B cells expressing the wt allele was dependent on the 5 component of the surrogate L chain, the development of B cells expressing the tg allele, including those with VH replacement, appeared to be 5 independent. We suggest that the unique CDR3 region of the tg-encoded µH chain is responsible for the 5 independence of tg-expressing B cells.

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 by an appropriation from the Commonwealth of Pennsylvania.

² Address correspondence and reprint requests to Dr. Melvin J. Bosma, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111. E-mail address: Melvin.Bosma{at}fccc.edu

³ Abbreviations used in this paper: cRSS, cryptic recombination signal sequence; β₂M, β₂-microglobulin; BM, bone marrow; SPL, spleen; tg, transgene; sd, site-directed; SL, surrogate light; wt, wild type; sIgM, surface IgM; sIgD, surface IgD; RF, reading frame; FL, fluorescein; SMART, switching mechanism at 5' end of the RNA transcript; MZ, marginal zone.

⁴ The online version of this article contains supplemental material.

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