Molecular underpinning of B-cell anergy.
A byproduct of the largely stochastic generation of a diverse B-cell specificity repertoire is production of cells that recognize autoantigens. Indeed, recent studies indicate that more than half of the primary repertoire consists of autoreactive B cells that must be silenced to prevent autoimmunity. While this silencing can occur by multiple mechanisms, it appears that most autoreactive B cells are silenced by anergy, wherein they populate peripheral lymphoid organs and continue to express unoccupied antigen receptors yet are unresponsive to antigen stimulation. Here we review molecular mechanisms that appear operative in maintaining the antigen unresponsiveness of anergic B cells. In addition, we present new data indicating that the failure of anergic B cells to mobilize calcium in response to antigen stimulation is not mediated by inactivation of stromal interacting molecule 1, a critical intermediary in intracellular store depletion-induced calcium influx.
Yarkoni
Yuval
Y
Integrated Department of Immunology, University of Colorado School of Medicine and National Jewish Health, Denver, CO, USA.
Getahun
Andrew
A
Cambier
John C
JC
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D017635:Clonal Anergy; D006801:Humans; D008213:Lymphocyte Activation; D018448:Models, Immunological; D015398:Signal Transduction