Immune memory responses are rapid and qualitatively distinct from primary responses. They typically develop in the presence of antigen-experienced memory T and B cells and preexisting antibodies. Although the contribution of T and B cells to recall responses is well defined, the contribution of antibody “memory” and the mechanisms by which preexisting antibodies modulate the development of germinal center (GC) and plasma cell responses is not precisely understood. Here, we report on mechanisms that mediate antibody enhancement of GC and plasmablast (PB) compartments, and the parallel process by which antibodies change the affinity threshold for B cell recruitment into immune responses. The data indicate that antibody-mediated enhancement of GC and PB responses is Fc gamma receptor (FcγR) dependent and largely complement receptor 1 and 2 (CR1/2) independent. In contrast, the reduction in the affinity threshold for GC entry is independent of both FcγRs and CR1/2.
Mechanisms of antibody-mediated enhancement of immune responses
Disclosures: L. Stamatatos reported a patent to 10,342,863 issued, a patent to 10,987,417 issued, a patent number 11,883,485 issued, and a patent to 12,551,549 issued. M.C. Nussenzweig is a member of the scientific advisory board of Celldex. Rockefeller University has licensed monoclonal antibodies 3BNC117 and 10-1074 to Gilead Pharmaceutical. No other disclosures were reported.
- Award Id(s): 5R37 AI037526,1UM1AI144462-01
- Award Id(s): CRI14522
Melissa Cipolla, Andrew J. MacLean, Brianna Hernandez, Gabriela S. Silva Santos, Leonidas Stamatatos, Anna Gazumyan, Harald Hartweger, Julia Merkenschlager, Stylianos Bournazos, Jeffrey V. Ravetch, Michel C. Nussenzweig; Mechanisms of antibody-mediated enhancement of immune responses. J Exp Med 7 September 2026; 223 (9): e20260305. doi: https://doi.org/10.1084/jem.20260305
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