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(CD79a)- and Ig
(CD79b)-Mediated Tonic Signaling for Bone Marrow B Cell Development and Peripheral B Cell Maturation1
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
The individual contribution of Ig
and Ig
for BCR-triggered fates is unclear. Prior evidence supports conflicting ideas concerning unique as well as redundant functions for these proteins in the context of BCR/pre-BCR signaling. Part of this ambiguity may reflect the recent appreciation that Ig and Ig participate in both Ag-independent (tonic) and Ag-dependent signaling. The present study undertook defining the individual requirement for Ig and Ig under conditions where only ligand-independent tonic signaling was operative. In this regard, we have constructed chimeric proteins containing one or two copies of the cytoplasmic domains of either Ig or Ig and Ig/Ig heterodimers with targeted Tyr
Phe modifications. The ability of these proteins to act as surrogate receptors and trigger early bone marrow and peripheral B cell maturation was tested in RAG2–/– primary pro-B cell lines and in gene transfer experiments in the µMT mouse model. We considered that the threshold for a functional activity mediated by the pre-BCR/BCR might only be reached when two functional copies of the Ig/Ig ITAM domain are expressed together, and therefore the specificity conferred by these proteins can only be observed in these conditions. We found that the ligand-independent tonic signal is sufficient to drive development into mature follicular B cells and both Ig and Ig chains supported formation of this population. In contrast, neither marginal zone nor B1 mature B cell subsets develop from bone marrow precursors under conditions where only tonic signals are generated.
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 funding from the Cancer Research Institute (to E.M.F.-P.) and the National Cancer Institute and National Institute of Allergy and Infectious Diseases (to J.G.M.).
2 Address correspondence and reprint requests to Dr. John G. Monroe, University of Pennsylvania School of Medicine, 421 Curie Boulevard, Biomedical Research Building II/III, Room 311, Philadelphia, PA 19104. E-mail address: monroej{at}mail.med.upenn.edu
3 Abbreviations used in this paper: SLC, surrogate L chain; BLNK, B cell linker; MZ, marginal zone; FO, follicular; WT, wild type; HA, hemagglutinin.
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  Y. Li, F. Chen, M. Putt, Y. K. Koo, M. Madaio, J. C. Cambier, P. L. Cohen, and R. A. Eisenberg B Cell Depletion with Anti-CD79 mAbs Ameliorates Autoimmune Disease in MRL/lpr Mice J. Immunol., September 1, 2008; 181(5): 2961 - 2972. [Abstract] [Full Text] [PDF]
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