B-1a and B-1b Cells Exhibit Distinct Developmental Requirements and Have Unique Functional Roles in Innate and Adaptive Immunity to S. pneumoniae
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B-1a and B-1b lymphocytes were found to exhibit specialized roles in providing immunity to Streptococcus pneumoniae and differ dramatically in their developmental requirements. Transgenic mice overexpressing CD19 (hCD19Tg) generated B-1a cells and natural antibodies that provided protection during infection, while CD19-deficient (CD19−/−) mice lacked B-1a cells, lacked natural antibodies, and were more susceptible to infection. By contrast, pneumococcal polysaccharide (PPS) immunization protected CD19−/− mice during lethal challenge, whereas hCD19Tg mice remained unprotected. This resulted from differences in the B-1b subset: the key population found to produce protective PPS-specific antibody in both wild-type and CD19−/− mice. Thus, CD19−/− mice generated B-1b cells and protective adaptive PPS-specific antibody responses, whereas hCD19Tg mice lacked B-1b cells and adaptive PPS-specific antibody responses. This reciprocal contribution of B-1a and B-1b subsets to innate and acquired immunity reveals an unexpected division of labor within the B-1 compartment that is normally balanced by their coordinated development.

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