RESUMO
B cells generate antibodies that are essential for immune protection, but their subgroups are poorly defined. Here, we perform undirected deep profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two subsets of marginal zone B (MZB) cells differing in cell surface and transcriptomic profiles, clonal relationships to other subsets, enrichment of genes in the NOTCH pathway, distribution bias within splenic marginal zone microenvironment, and immunoglobulin repertoire diversity and hypermutation frequency. Each subset is present in spleen, gut-associated lymphoid tissue, mesenteric lymph nodes, and blood. MZB cells and the lineage from which they are derived are depleted in lupus nephritis. Here, we show that this depletion is of only one MZB subset. The other remains unchanged as a proportion of total B cells compared with health. Thus, it is important to factor MZB cell heterogeneity into studies of human B cell responses and pathology.
Assuntos
Linfócitos B , Tecido Linfoide , Humanos , Ativação Linfocitária , Contagem de Linfócitos , BaçoRESUMO
Our understanding of the B-cell subsets found in human blood and their functional significance has advanced greatly in the past decade. This has been aided by the evolution of high dimensional phenotypic tools such as mass cytometry and single-cell RNA sequencing which have revealed heterogeneity in populations that were previously considered homogenous. Despite this, there is still uncertainty and variation between studies as to how B-cell subsets are identified and named. This review will focus on the most commonly encountered subsets of B cells in human blood and will describe gating strategies for their identification by flow and mass cytometry. Important changes to population frequencies and function in common inflammatory and autoimmune diseases will also be described.
