| First Author | Cumpelik A | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 6 | Pages | 757-768 |
| PubMed ID | 34031614 | Mgi Jnum | J:314460 |
| Mgi Id | MGI:6740249 | Doi | 10.1038/s41590-021-00926-0 |
| Citation | Cumpelik A, et al. (2021) Dynamic regulation of B cell complement signaling is integral to germinal center responses. Nat Immunol 22(6):757-768 |
| abstractText | Maturation of B cells within germinal centers (GCs) generates diversified B cell pools and high-affinity B cell antigen receptors (BCRs) for pathogen clearance. Increased receptor affinity is achieved by iterative cycles of T cell-dependent, affinity-based B cell positive selection and clonal expansion by mechanisms hitherto incompletely understood. Here we found that, as part of a physiologic program, GC B cells repressed expression of decay-accelerating factor (DAF/CD55) and other complement C3 convertase regulators via BCL6, but increased the expression of C5b-9 inhibitor CD59. These changes permitted C3 cleavage on GC B cell surfaces without the formation of membrane attack complex and activated C3a- and C5a-receptor signals required for positive selection. Genetic disruption of this pathway in antigen-activated B cells by conditional transgenic DAF overexpression or deletion of C3a and C5a receptors limited the activation of mechanistic target of rapamycin (mTOR) in response to BCR-CD40 signaling, causing premature GC collapse and impaired affinity maturation. These results reveal that coordinated shifts in complement regulation within the GC provide crucial signals underlying GC B cell positive selection. |
