The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/9/749/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 6, September 20, 1999 749-756

Original Article

Distinct Signal Thresholds for the Unique Antigen Receptor–Linked Gene Expression Programs in Mature and Immature B Cells

Robert J. Benschopa, Doron Melameda, David Nemazeea,b, and John C. Cambiera,b

a Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center
b Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206
Dept. of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206.303-398-1225303-398-1325

cambierj{at}njc.org

Although it is well established that immature B lymphocytes are exquisitely sensitive to tolerance induction compared with their mature counterparts, the molecular basis for this difference is unknown. We demonstrate that signaling by B cell antigen receptors leads to distinct and mutually exclusive biologic responses in mature and immature B cells: upregulation of CD86, CD69, and MHC class II in mature cells and receptor editing in immature cells. These responses can be induced simply by elevation of intracellular free calcium levels, as occurs after receptor aggregation. Importantly, induction of immature B cell responses requires much smaller increases in intracellular free calcium than does induction of mature B cell responses. These differences in biologic response and sensitivity to intracellular free calcium likely contributes to selective elimination at the immature stage of even those B cells that express low affinity for self-antigens.

Key Words: signal transduction • B cells • receptor editing • B cell antigen receptor • development

1used in this paper: BCR, B cell antigen receptor; BM, bone marrow; HEL, hen egg lysozyme; ITAM, immunoreceptor tyrosine-based activation motif; PLC, phospholipase C; RAG, recombinase activator gene; Tg, transgenic

D. Melamed's current address is Technion, Haifa 31096, Israel. D. Nemazee's current address is The Scripps Research Institute, La Jolla, CA 92057.

© 1999 The Rockefeller University Press


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