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AIRRC5 - Human B cell Effector Pathways (Autoimmune, Infectious and Vaccination responses) (I. Sanz)

Session from the "AIRR Community Meeting V – Zooming in to the AIRR Community!" (December 8-10, 2020) The meeting covers progress reports from the AIRR-C Working Groups & Sub-committees, two scientific sessions (including four short talks chosen from the posters), two interactive poster sessions and four live software tool demonstrations. https://www.antibodysociety.org/the-a... B-cell repertoire response to COVID-19 - Moderated by Jamie Scott (Jamie Scott, Professor Emerita, Simon Fraser University) Understanding Human B cell Effector Pathways. Implications for Autoimmune, Infectious and Vaccination Responses. Ignacio Sanz Professor, Depts of Medicine and Pediatrics, Emory University School of Medicine Human effector B cell responses may proceed through different differentiation pathways, including newly described extra-follicular and conventional germinal center and memory responses, potentially leading to different types of antibody responses. We have recently shown that effector B cell responses of different intensity and quality characterize patients with severe COVID-19 infection, relative to milder infections. Thus, while the former group has enhanced EF responses highly reminiscent of those of patients with severe SLE, the latter is characterized by the expansion of a subset of transitional B cells. From a BCR repertoire standpoint, the EF response demonstrates both a high frequency of unmutated/low mutated lineages but also a significant degree of somatic hypermutation and isotype switch. These maturational processes were frequently detected within the same clonal lineages and included frequent VH4-34-based lineages, thereby suggesting an important early contribution to a human primary viral infection of mechanisms conventionally ascribed to memory responses. The clinical and immunological implications of these findings will be discussed.