Low-level signaling generated by FcgammaRIIB-B cell receptor co-ligation establishes a state of global B cell receptor nonresponsiveness.
In addition to the stimulatory, antigen-specific B cell receptor (BCR), B lymphocytes also express multiple inhibitory receptors, including Fc gamma receptor type IIB (FcgammaRIIB). Moreover, many laboratories have demonstrated that co-ligation of BCR molecules to inhibitory FcgammaRIIB molecules with high concentrations (10-15 microg/ml) of ligand results in altered BCR signaling. However, there are no reports on the effect of low concentrations of ligand on BCR-FcgammaRIIB co-ligation and subsequent signaling. This knowledge will be critical for optimizing the in vivo use of such reagents. Accordingly, the effect of low ligand concentration on the level of BCR-FcgammaRIIB co-ligation and subsequent BCR signaling was analyzed. The results demonstrate that co-ligation of BCR and FcgammaRIIB molecules at low concentrations (0.5-1.5 microg/ml) of cross-linking reagent, establishes a condition that prevents the B cell from responding to subsequent stimulation, even when the initial exposure to cross-linking reagent fails to generate a calcium flux. Moreover, analysis of the effect of BCR-FcgammaRIIB co-ligation in cells expressing a nonsignaling competent BCR suggest that FcgammaRIIB-mediated inhibition of BCR signaling requires co-ligation of FcgammaRIIB with signaling competent BCR molecules. These results suggest that in vivo treatments with low levels of BCR-FcgammaRIIB cross-linking reagent can induce BCR-FcgammaRIIB co-ligation and establish a condition of B cell nonresponsiveness.
Preissler
Mark T
MT
Albany Medical College, Center for Immunology and Microbial Disease, Albany, New York 12208, USA.
Kaiser
Laura
L
Drake
James R
JR
Gosselin
Edmund J
EJ
D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D008213:Lymphocyte Activation / Q000276:immunology / Q000502:physiology; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology* / Q000502:physiology; D013997:Time Factors
D015703:Antigens, CD; D003432:Cross-Linking Reagents; C080571:Fc gamma receptor IIB; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D002118:Calcium