Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues (preprint)

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells encoding humoral immune memory. We evaluated convergent antigen-specific antibody genes of similar sequences shared between individuals in pediatric and adult blood, and deceased organ donor tissues. B cell memory varied for different pathogens. Polysaccharide antigen-specific clones were not exclusive to the spleen. Adults convergent clones often express mutated IgM or IgD in blood and are class-switched in lymphoid tissues; in contrast, children have abundant class-switched convergent clones in blood. Consistent with serological reports, pre-pandemic children had class-switched convergent clones to SARS-CoV-2, enriched in cross-reactive clones for seasonal coronaviruses, while adults showed few such clones in blood or lymphoid tissues. These results extend age-related and anatomical mapping of human humoral pathogen-specific immunity. One Sentence SummaryChildren have elevated frequencies of pathogen-specific class-switched memory B cells, including SARS-CoV-2-binding clones.

B cell clonal expansion and convergent antibody responses to SARS-CoV-2 (preprint)

During virus infection B cells are critical for the production of antibodies and protective immunity. Establishment of a diverse antibody repertoire occurs by rearrangement of germline DNA at the immunoglobulin heavy and light chain loci to encode the membrane-bound form of antibodies, the B cell antigen receptor. Little is known about the B cells and antigen receptors stimulated by the novel human coronavirus SARS-CoV-2. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of V genes, and extensive activation of IgG and IgA subclasses without significant somatic mutation. We detect expansion of B cell clones as well as convergent antibodies with highly similar sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. A shared convergent B cell clonotype in SARS-CoV-2 infected patients was previously seen in patients with SARS. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.