tetano
Editor, Senior Moderator
Blood. 2011 Dec 5. [Epub ahead of print]
BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation.
Wensveen FM, Derks IA, van Gisbergen KP, de Bruin AM, Meijers JC, Yigittop H, Nolte MA, Eldering E, van Lier RA.
Source
Department of Experimental Immunology, Academic Medical Center, Amsterdam, Netherlands;
Abstract
The efficiency of humoral immune responses depends on the selective outgrowth of B cells and plasmacells that produce high affinity antibodies. The factors responsible for affinity maturation of B cell clones in the germinal center (GC) have been well established but selection mechanisms that allow clones to enter the GC are largely unknown. Here we identify apoptosis, regulated by the pro-apoptotic BH3-only member Noxa (Pmaip1), as a critical factor for the selection of high-affinity clones during B cell expansion after antigen triggering. Noxa is induced in activated B cells and its ablation provides a survival advantage both in vitro and in vivo. After immunization or influenza infection, Noxa(-/-) mice display enlarged GC's in which B cells with reduced antigen affinity accumulate. As a consequence, Noxa(-/-) mice mount low affinity antibody responses compared to WT animals. Importantly, the low affinity responses correlate with increased immunoglobulin diversity, and cannot be corrected by booster immunization. Thus, normally elimination of low affinity cells favors outgrowth of the remaining high affinity clones, and this is mandatory for the generation of proper antibody responses. Manipulation of this process may alter the breadth of antibody responses following immunization.
PMID:
22144184
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22144184
BH3-only protein Noxa regulates apoptosis in activated B cells and controls high-affinity antibody formation.
Wensveen FM, Derks IA, van Gisbergen KP, de Bruin AM, Meijers JC, Yigittop H, Nolte MA, Eldering E, van Lier RA.
Source
Department of Experimental Immunology, Academic Medical Center, Amsterdam, Netherlands;
Abstract
The efficiency of humoral immune responses depends on the selective outgrowth of B cells and plasmacells that produce high affinity antibodies. The factors responsible for affinity maturation of B cell clones in the germinal center (GC) have been well established but selection mechanisms that allow clones to enter the GC are largely unknown. Here we identify apoptosis, regulated by the pro-apoptotic BH3-only member Noxa (Pmaip1), as a critical factor for the selection of high-affinity clones during B cell expansion after antigen triggering. Noxa is induced in activated B cells and its ablation provides a survival advantage both in vitro and in vivo. After immunization or influenza infection, Noxa(-/-) mice display enlarged GC's in which B cells with reduced antigen affinity accumulate. As a consequence, Noxa(-/-) mice mount low affinity antibody responses compared to WT animals. Importantly, the low affinity responses correlate with increased immunoglobulin diversity, and cannot be corrected by booster immunization. Thus, normally elimination of low affinity cells favors outgrowth of the remaining high affinity clones, and this is mandatory for the generation of proper antibody responses. Manipulation of this process may alter the breadth of antibody responses following immunization.
PMID:
22144184
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22144184