Regulation of Murine Splenic B Cell CR3 Expression by Complement Component 3

Abstract

Complement component C3 has established roles in both innate and adaptive immune responses. C3 cleavage products function in B cell activation through the complement receptors CD21/35. Phenotypes of Ab production between CD21/35−/− and C3−/− mice are not always congruent, implicating additional roles for C3 in B cell responses. To further characterize complement and complement receptors, we have identified a role for C3 in the regulation of CR3 on splenic B cells. Splenic B2 cells are not defined as expressing CR3, yet the analysis of splenic B cells from C3−/− animals demonstrate cell surface expression of CR3. B cells from both wild-type (WT) and C3−/− animals express CR3/CD11b/Itgam (integrin α M) gene transcripts although the level of such transcripts is 2- to 3-fold higher in B cells from the C3−/− animal vs WT cells. C3−/− and WT animals have similar B cell subpopulations with identical CR3 expression on B220− cells from the spleen, marrow, and lymph nodes. The C3-deficient environment is responsible for altered CR3 expression as WT splenic B cells transferred into C3−/− animals expressed cell surface CR3 within 48 h while transfer of C3−/− splenic B cells into WT animals depressed surface expression of CR3. Furthermore, transfer of C3-producing splenic macrophages into C3−/− mice depressed CR3 expression by resident B cells. These data suggest a role for C3 in influencing the level of expression of CR3 by modulating the transcript levels encoding the CD11b α integrin protein.