PhD student Johns Hopkins Bloomberg Sch. of Pub. Hlth. Baltimore, Maryland, United States
Disclosure(s):
Beatriz Silva Lopes, B.S, ScM: No financial relationships to disclose
Introduction/Rationale: Most if not all the IgM secreted early after Influenza virus infection by B-1 and B-2 cells is derived from antibody-secreting cells (ASCs) developing in rapidly forming extrafollicular (EF) B cell responses. We previously demonstrated that the lack of the early-derived IgM significantly reduces the later-induced IgG response to influenza A virus (IAV) infection. The mechanisms underlying this effect on IgG remain to be fully explored. Here we hypothesize that EF-derived IgM affects antigen retention and stimulation of germinal center (GC) B cells, promoting stronger selection for memory and plasma cell differentiation in GCs.
Methods: Flow cytometry, ELISPOT, ELISA.
Results: To investigate the impact of reduced EF response output on GC functionality, we infected secreted IgM knockout (s-IgM KO) mice with IAV and analyzed the draining mediastinal lymph nodes (medLN) for alterations in GC B cell frequencies at day 14 post-infection. Our initial studies demonstrate significant reductions in both frequency and total numbers of GC B cells in s-IgM KO mice compared to wild-type (WT) controls. Moreover, we found that s-IgM KO mice harbored significantly fewer CD80+,CD73+ , Influenza hemagglutinin (HA)-specific memory B cells at 30 days post infection (p.i) and decreased HA+ plasma cells in the bone marrow compared to WT mice at 45 days p.i. Antigen-specific serum and bone marrow antibody levels were assessed by ELISA and ELISPOT, and female s-IgMKO mice showed a reduction in IgG levels compared to WT after 45 days p.i.
Conclusion: Collectively, this data suggests that early EF-derived IgM responses are critical to support maximal GC outputs. Understanding these mechanisms may provide valuable insights for optimizing vaccine strategies against IAV infections.
