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

doi:10.1084/jem.190.6.749

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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

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

Robert J. Benschop^a, Doron Melamed^a, David Nemazee^a,b, and John C. Cambier^a,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

Correspondence to: John C. Cambier, Dept. of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Tel:303-398-1325 Fax:303-398-1225 E-mail:cambierj{at}njc.org.

Although it is well established that immature B lymphocytesare exquisitely sensitive to tolerance induction compared withtheir mature counterparts, the molecular basis for this differenceis unknown. We demonstrate that signaling by B cell antigenreceptors leads to distinct and mutually exclusive biologicresponses in mature and immature B cells: upregulation of CD86,CD69, and MHC class II in mature cells and receptor editingin immature cells. These responses can be induced simply byelevation of intracellular free calcium levels, as occurs afterreceptor aggregation. Importantly, induction of immature B cellresponses requires much smaller increases in intracellular freecalcium than does induction of mature B cell responses. Thesedifferences in biologic response and sensitivity to intracellularfree calcium likely contributes to selective elimination atthe immature stage of even those B cells that express low affinityfor self-antigens.

Key Words: signal transduction, B cells, receptor editing, B cell antigenreceptor, development

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