CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22–/– mice generate significantly impaired Ab responses to T cell–independent type 2 (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags that elicit poor T cell help and activate BCR signaling via multivalent epitope crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B cell development/maintenance in CD22–/– mice. However, mice expressing a mutant form of CD22 unable to bind sialic acid ligands generated normal TI-2 Ab responses, despite significantly reduced MZ B cells. Moreover, mice treated with CD22 ligand–binding blocking mAbs, which deplete MZ B cells, had little effect on TI-2 Ab responses. We therefore investigated the effects of CD22 deficiency on B-1b cells, an innate-like B cell population that plays a key role in TI-2 Ab responses. B-1b cells from CD22–/– mice had impaired BCR-induced proliferation and significantly increased intracellular Ca2+ concentration responses following BCR crosslinking. Ag-specific B-1b cell expansion and plasmablast differentiation following TI-2 Ag immunization was significantly impaired in CD22–/– mice, consistent with reduced TI-2 Ab responses. We generated CD22–/– mice with reduced CD19 levels (CD22–/–CD19+/–) to test the hypothesis that augmented B-1b cell BCR signaling in CD22–/– mice contributes to impaired TI-2 Ab responses. BCR-induced proliferation and intracellular Ca2+ concentration responses were normalized in CD22–/–CD19+/– B-1b cells. Consistent with this, TI-2 Ag-specific B-1b cell expansion, plasmablast differentiation, survival, and Ab responses were rescued in CD22–/–CD19+/– mice. Thus, CD22 plays a critical role in regulating TI-2 Ab responses through regulating B-1b cell signaling thresholds.
from The Journal of Immunology current issue http://ift.tt/2om6qfc
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