An atlas of B-cell clonal distribution in the human body

Abstract

B cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B cell clones are distributed in the body, we sequenced 933,427 B cell clonal lineages and mapped them to 8 different anatomic compartments in 6 human organ donors. We show that large B cell clones partition into two broad networks—one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

Indeterminate pediatric acute liver failure is uniquely characterized by a CD103+CD8+ T‐cell infiltrate

“…A,B) and by measuring percent overlapping clones between the duplicates of each sample, which is expected to be higher if specific clones dominate the specimen (Fig. C) . By both measures, iPALF cases showed significantly increased clonality compared to dPALF and control cases ( P < 0.01).…”

Gut and Liver B Cells of Common Clonal Origin in Primary Sclerosing Cholangitis–Inflammatory Bowel Disease

“…As extensive sharing of clonotypes among tissues within the gastrointestinal tract has been reported, our results may not be unique to PSC‐IBD, and the expansion of private clonotypes across the gut–liver axis may be a common phenomenon in many disease settings. Paired gut and liver samples from IBD patients without PSC would serve as the ideal control to address this question; however, these patients do not undergo routine liver biopsy or liver transplantation and thus liver samples are not typically available.…”

B lymphocytes confer immune tolerance via cell surface GARP-TGF-β complex

“…It makes teleological sense for PP B cells therefore to be equipped with more robust peripheral tolerance mechanisms, such as the GARP-TGF-β axis. A recent comprehensive study of the B cell clonal distribution in humans revealed two broad clonal networks: one encompassing the blood, bone marrow, spleen, and lungs, and the other that is restricted to tissues within the gastrointestinal tract (75). The group observed that the GI tract clones have higher frequencies of somatic hypermutation, which suggests a biological relevance for the heightened importance for GARP in the PP immune compartment in order to tolerize self and oral antigens.…”