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Ig Allotypic Inclusion Does Not Prevent B Cell Development or Response¹

Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, CO 80206

B cells expressing two different Ig L chains (allotype included) have been occasionally observed. To determine frequency and function of these cells, we have analyzed gene-targeted mice that carry a human and a mouse Igk C region genes. Using different methodologies, we found that cells expressing two distinct -chains were 1.4–3% of all B cells and that they were present in the follicular, marginal zone, and B1 mature B cell subsets. When stimulated in vitro with anti-IgM, dual surface-positive cells underwent activation that manifested with cell proliferation and/or up-regulation of activation markers and similar to single -expressing B cells. Yet, when activated by divalent reagents that bound only one of the two -chains, dual B cells responded suboptimally in vitro, most likely because of reduced Ag receptor cross-linking. Nonetheless, dual B cells participated in a SRBC-specific immune response in vivo. Finally, we found that Ig allotype-included B cells that coexpress autoreactive and nonautoreactive Ag receptors were also capable of in vitro responses following BCR aggregation. In summary, our studies demonstrate that Ig allotype-included B cells are present in the mouse mature B cell population and are responsive to BCR stimulation both in vitro and in vivo. Moreover, because in vitro activation in response to anti-IgM was also observed in cells coexpressing autoreactive and nonautoreactive Abs, our studies suggest a potential role of allotype-included B cells in both physiological and pathological immune responses.

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 the National Institutes of Health Grant AI052310.

² Address correspondence and reprint requests to Dr. Roberta Pelanda, Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, 1400 Jackson Street, Denver, CO 80206.

³ Abbreviations used in this paper: ASC, Ab-secreting cell; AP, alkaline phosphatase; FO, follicular; hIg, human Ig; int, intermediate; MZ, marginal zone; m, mouse; h, human.

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