• Memory and Effector B cell Responses to Viral and Intracellular Bacterial Infection

      Gary M. Winslow; Newell, Krista (2021)
      Infection with an intracellular pathogen presents the host with the immunological challenge of intracellular access and of clearing infection without excessive damage to host tissues. This challenge was long thought to be addressed primarily by cell-mediated immunity, but is now known to include a significant humoral component. To better understand the B cell-mediated contribution to intracellular pathogen control, we investigated memory and effector B cell responses to the intracellular bacterial pathogen Ehrlichia muris, and SARS-CoV-2 infection. B cells expressing the transcription factor T-bet were identified in both mice and humans, and T-bet played an important role in directing antibody class switch recombination, but not in the generation of memory B cells during E. muris infection. T-bet expression was identified in cells resembling murine B-1 B cells, an innate-like subset of B cells important for early T cell-independent B cell responses. These results suggest that T-bet expression in B-1 B cells may contribute to their participation in the early B cell response to murine intracellular bacterial infection. Following human SARS-CoV-2 infection, we revealed that in addition to the canonical class-switched B cell memory response, the presence of a substantial pool of peripheral blood unswitched IgM+ memory B cells was correlated with reduced symptom duration and enhanced generation of antigen-specific antibody. These IgM+ memory B cells were stable, unlike the contracting plasmablast response. These studies underscore the importance of innate and unswitched B cell subsets to the functional plasticity of the humoral response and contribute to our understanding of correlates of innate protection and adaptive immunity.