Oral Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2026

Antibody-mediated regulation of B cell responses to vaccination (#34)

Birk Evavold 1 , Katherine McIntire 1 , Julian Zhou 1 , Wafaa Alsoussi 1 , Aaron Schmitz 1 , Alexandria Sturtz 1 , Hiromi Muramatsu 2 , Fangjie Han 1 , Seo-kyung Kim 1 , Jonathan Perez 1 , Jackson Turner 1 , Norbert Pardi 2 , Ali H Ellebedy 1
  1. Washington University, St. Louis, MO, United States
  2. University of Pennsylvania, Philadelphia, PA, USA

Following vaccination, responding B cells differentiate into antibody-secreting plasmablasts or are recruited into the germinal center reaction. In the germinal center, antigen-specific B cells undergo affinity maturation, a process critical for creating durable, protective B cell responses to pathogens. Therefore, investigating the factors that regulate the magnitude and persistence of the germinal center reaction is essential to understand how effective B cell responses to vaccination are generated. We hypothesize that antibodies produced early in the immune response by plasmablasts regulate the germinal center reaction. To test this hypothesis, we created a novel mouse model with inducible cessation of IgG1 antibody secretion. Using this mouse, we demonstrate that antibodies produced in a primary response to an mRNA-LNP vaccine alter germinal center B cell dynamics. We demonstrate that depletion of IgG1 results in a more robust germinal center B cell response during germinal center resolution.  Furthermore, by delaying the depletion of antibodies, we demonstrate that antibodies produced early in the immune response are responsible for this regulation implicating a role for plasmablast-derived antibodies in shaping the primary B cell response. Additionally, we show an increased antigen-specific memory B cell population following antibody depletion, likely due to the augmented output from the increased germinal center response. To uncover the mechanism through which IgG1 regulated the GC magnitude, we utilized a passive immunization approach. We observed that addition of antigen-specific IgG1 antibodies reduced and reverted the GC magnitude; however, addition of antigen-specific IgG1 antibodies lacking Fc receptor interactions maintained GC magnitude differences, suggesting that IgG1 regulates GC magnitude via Fc receptor-mediated inhibition. In summary, these results demonstrate that early IgG1 antibodies regulate GC B cell magnitude and MBC progeny through interactions with Fc receptors.