While human B cells have been extensively studied, most reports have used peripheral blood as a source. Here we have used a unique tissue resource derived from healthy organ donors to deeply characterize human B cell compartments across multiple tissues and donors. These data sets revealed that B cells in the blood are not in homeostasis with compartments in other tissues. We found striking donor-to-donor variability in the frequencies and isotype of CD27+ memory B cells (MBC). A comprehensive Ab-based screen revealed markers of MBC and allowed identification of novel MBC subsets with distinct function defined by surface expression of CD69 and CD45RB. We defined a tissue-resident MBC phenotype that was predominant in the gut but absent in blood. RNA sequencing of MBC subsets from multiple tissues revealed a tissue-resident MBC gene signature as well as gut and spleen-specific signatures. Overall, these studies provide novel insights into the nature and function of human B cell compartments across multiple tissues.
Optimal vaccines are needed for sustained suppression of SARS‐CoV‐2 and other novel coronaviruses. Here, we developed a recombinant type 5 adenovirus vector encoding the gene for the SARS‐CoV‐2 S1 subunit antigen (Ad5.SARS‐CoV‐2‐S1) for COVID‐19 immunization and evaluated its immunogenicity in mice. A single immunization with Ad5.SARS‐CoV‐2‐S1 via S.C. injection or I.N delivery induced robust antibody and cellular immune responses. Vaccination elicited significant S1‐specific IgG, IgG1, and IgG2a endpoint titers as early as 2 weeks, and the induced antibodies were long lasting. I.N. and S.C. administration of Ad5.SARS‐CoV‐2‐S1 produced S1‐specific GC B cells in cervical and axillary LNs, respectively. Moreover, I.N. and S.C. immunization evoked significantly greater antigen‐specific T‐cell responses compared to unimmunized control groups with indications that S.C. injection was more effective than I.N. delivery in eliciting cellular immune responses. Mice vaccinated by either route demonstrated significantly increased virus‐specific neutralization antibodies on weeks 8 and 12 compared to control groups, as well as BM antibody forming cells (AFC), indicative of long‐term immunity. Thus, this Ad5‐vectored SARS‐CoV‐2 vaccine candidate showed promising immunogenicity following delivery to mice by S.C. and I.N. routes of administration, supporting the further development of Ad‐based vaccines against COVID‐19 and other infectious diseases for sustainable global immunization programs.
Asthma is an immune-mediated heterogeneous disease. Current type-2 biomarkers provide limited understanding of underlying pathobiology or therapeutic guidance. Using a multi-omics approach, Camiolo et al. identify two clusters of severe asthma patients with similar type-2 biomarkers but with strikingly distinct immune profiles and associated biological pathways.
We have performed a comprehensive analysis of human lymphoid tissue from relatively inaccessible sites including SPL, BM and LN from normal donors. Most of what is known about human B cells comes from blood, a tissue that contains only ~2% of the immune cells in the body. Examination of different tissues from 14 independent donors reveals for the first time the global B cell population structure. We performed unbiased computational clustering on samples stained with antibodies to markers indicative of antigen experience, activation status, and tissue retention. We found that the population structure of splenic B cells is remarkably conserved across a large number of donors who vary by age, gender, environment and history of pathogen exposure. By contrast, blood B cell composition is highly individualized with respect to each donor while BM has a relatively uniform population structure with some individual tailoring. Comparison of paired tissues within individuals further demonstrates that SPL and blood contain largely non-overlapping populations, suggesting geographic segregation of B cell subsets within each person. Recently published Ig clonal tracking studies from this donor cohort demonstrates partitioning of B cell clonal sharing into two broad networks, one across blood rich tissues and the other restricted to portions of the GI tract. Knowledge about the mechanisms that direct the trafficking and retention of discrete B cell subsets to specific tissues has direct implication to how infections are controlled throughout the body. Our findings constitute the basis for a geographic understanding of B cell population structure that will inform studies on the human humoral immune response.
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