Complement receptors CD21/35 link innate and protective immunity during Streptococcus pneumoniae infection by regulating IgG3 antibody responses.
The CD21/35 receptor provides an important link between innate and adaptive immunity. Its importance during protective immune responses to encapsulated extracellular bacteria was assessed using a new line of mice completely deficient in CD21/35 expression (CD21/35(-/-)). CD21/35 expression was essential for the rapid trapping of C3dg-antigen complexes by B cells in vivo, especially in splenic marginal zones. Despite normal B cell development in CD21/35(-/-) mice, T cell-independent and -dependent antibody responses to low-dose antigens were significantly decreased, with a striking impairment in IgG3 responses. Accordingly, CD21/35(-/-) mice were more susceptible to acute lethal Streptococcus pneumoniae infection. Thus, CD21/35 expression is critical for early protective antibody responses to lethal pathogens that rapidly multiply and quickly overwhelm the immune system.
Haas, KM; Hasegawa, M; Steeber, DA; Poe, JC; Zabel, MD; Bock, CB; Karp, DR; Briles, DE; Weis, JH; Tedder, TF
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