The Magnitude of the Secondary B Cell Response is Shaped by Pre-Existing Antibodies Rather Than the Number of Memory B Cells Present.

Clonal expansion of memory lymphocytes after each antigen encounter is the primary mechanism for amplifying immunity. For most vaccines, boosters are common practice and are expected to stimulate proliferation of pre-existing memory B cells (B), thereby expanding the antigen-specific B pool, along with driving their differentiation into antibody-producing plasma cells that replenish antibody titers. It is widely assumed that the number of B present in the body prior to administration of a booster vaccination will define the magnitude of the ensuing response. By comparing B frequencies and antibody titers in the same individuals after primary and secondary vaccination with SARS-CoV-2 Spike (S-antigen)-encoding mRNA, we found that expansion of B and the relative increase of the secondary antibody response were not determined by the number of B measured before the second vaccine inoculation. Instead, both were inversely correlated with levels of S-antigen-specific serum IgG prior to the secondary antigen exposure. Collectively, these data suggest that secondary B cell responses are constrained by antibody feedback inhibition of B, rather than their scarcity.

© 2026 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.

PMID: 43016051