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The Journal of Immunology, 1998, 161: 252-259.
Copyright © 1998 by The American Association of Immunologists

Role of µ Heavy Chain in B Cell Development. I. Blocked B Cell Maturation But Complete Allelic Exclusion in the Absence of Ig{alpha}/ß1

Frank E. Cronin*, Ming Jiang{dagger}, Abul K. Abbas* and Stephan A. Grupp2,{dagger}

* Immunology Research Division, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115; and {dagger} Division of Pediatric Oncology, Children’s Hospital of Philadelphia, Philadelphia, PA 19104

There is good evidence for a signaling role played by Ig heavy chain in the developmental transition through the pre-B cell stage. We have previously described signal-capable or signal-incapable mutants of µ heavy chain in which a signaling defect is caused by failure to associate with the Ig{alpha}/ß heterodimer. To further characterize the role of Ig heavy chain-mediated signaling in vivo, as well as in B cell development and allelic exclusion, we have created transgenic mice in which the B cells express these signal-capable and signal-incapable mutant µ chains. Failure of µ to signal via Ig{alpha}/ß results in a block in B cell development in mice expressing the signal-incapable µ. A small number of B cells in these animals do escape the developmental block and are expressed in the spleen and the periphery as B220+ transgenic IgM+ cells. These cells respond to LPS by proliferating but show no response to T-independent-specific Ag. In contrast, B cells expressing the signal-capable B cell receptor show a strong signaling response to Ag-specific stimulus. There is no Ig{alpha} seen in association with signal-deficient IgM. Thus, the B cell receptor complex is not assembled, and no signal can be delivered. Despite the block in developmental signaling, allelic exclusion is complete. There is no detectable coexpression of transgenic IgM and endogenous murine IgM, nor is there rearrangement of the endogenous heavy chain genes. This suggests that differing signaling mechanisms are responsible for the developmental transition and allelic exclusion and thus allows for separate examination of these signaling mechanisms.




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