Specific in vivo deletion of B-cell subpopulations expressing human immunoglobulins by the B-cell superantigen protein L.
Some pathogens have evolved to produce proteins, called B-cell superantigens, that can interact with human immunoglobulin variable regions, independently of the combining site, and activate B lymphocytes that express the target immunoglobulins. However, the in vivo consequences of these interactions on human B-cell numbers and function are largely unknown. Using transgenic mice expressing fully human immunoglobulins, we studied the consequences of in vivo exposure of protein L of Peptostreptococcus magnus with human immunoglobulins. In the mature pool of B cells, protein L exposure resulted in a specific reduction of splenic marginal-zone B cells and peritoneal B-1 cells. Splenic B cells exhibited a skewed light-chain repertoire consistent with the capacity of protein L to bind specific kappa gene products. Remarkably, these two B-cell subsets are implicated in innate B-cell immunity, allowing rapid clearance of pathogens. Thus, the present study reveals a novel mechanism that may be used by some infectious agents to subvert a first line of the host's immune defense.
Viau
Muriel
M
Institut National de Sante et de Recherche Medicale (INSERM U 430), Immunopathologie Humaine, 75006 Paris, France.
Longo
Nancy S
NS
Lipsky
Peter E
PE
Björck
Lars
L
Zouali
Moncef
M
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000097:blood; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010462:Peptostreptococcus / Q000378:metabolism / Q000472:pathogenicity*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000276:immunology*
D001426:Bacterial Proteins; C055047:Ig L-binding protein, Peptostreptococcus; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007136:Immunoglobulins; D018089:Superantigens