| First Author | Haas KM | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 5 | Pages | 1671-1681 |
| PubMed ID | 29374074 | Mgi Jnum | J:258424 |
| Mgi Id | MGI:6117923 | Doi | 10.4049/jimmunol.1701578 |
| Citation | Haas KM, et al. (2018) CD22 Promotes B-1b Cell Responses to T Cell-Independent Type 2 Antigens. J Immunol 200(5):1671-1681 |
| abstractText | 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 Ca(2+) 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 Ca(2+) 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. |
