Journal Article

IgM+IgD− B cells in human gut-associated lymphoid tissue have memory features and give rise to IgM+ and IgA+ antibody-secreting cells

Meng, Wenzhao, Knight, Katherine L., Bukhari, Ameera M., Rosenfeld, Aaron M., Prak, Eline T. Luning

2025

Overview

Human IgM + B cells vary in their surface levels of IgD, with the major circulating population of IgM + IgD + cells and a minor population (< 5%) of IgM + IgD − cells. In contrast, in gut-associated lymphoid tissue (GALT) derived from individuals undergoing tonsillectomy or appendectomy, IgM + IgD − B cells constitute ~ 30% of B cells. IgM + IgD − cells isolated from both tonsil and appendix lack plasma cell and B1 cell markers, and approximately 50% express the memory marker CD27. Functionally, GALT IgM + IgD − cells spontaneously secrete IgM, and class-switch to IgA in response to both T-dependent and T-independent stimulation ex-vivo. Immune repertoire profiling reveals that GALT IgM + IgD − cells exhibit lower levels of VH4-34 rearrangements, higher levels of somatic hypermutation, shorter CDR3 sequences and greater clonal overlap with switch memory cells than IgM + IgD + cells. Furthermore, clonal lineage analysis reveals that IgM + IgD − clones can include class-switched sequence variants. These findings suggest a maturational scheme starting from CD27 − IgM + IgD + B cells to CD27 + IgM + IgD + , and then to CD27 − IgM + IgD − , and finally to CD27 + IgM + IgD − B cells. In sum, IgM + IgD − B cells in the mucosa have memory features, give rise to class-switched memory B cells and antibody-secreting cells, and likely contribute significantly to the IgA repertoire in human GALT.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/250 / 631/250/1619/40 / Antibody-Producing Cells - immunology / Antibody-Producing Cells - metabolism / Antigens / Appendectomy / B cells / B-Lymphocytes - immunology / B-Lymphocytes - metabolism / CD27 antigen / Cells / Class switching / Complementarity-determining region 3 / Flow cytometry / Genotype & phenotype / Gut-associated lymphoid tissue (GALT) / Gut-associated lymphoid tissues / Humanities and Social Sciences / Humans / IgM+ B cells / Immunoglobulin A / Immunoglobulin A - immunology / Immunoglobulin A - metabolism / Immunoglobulin Class Switching / Immunoglobulin D / Immunoglobulin D - immunology / Immunoglobulin D - metabolism / Immunoglobulin M / Immunoglobulin M - immunology / Immunoglobulin M - metabolism / Immunologic Memory / Immunological memory / Lymphocytes B / Lymphoid tissue / Lymphoid Tissue - cytology / Lymphoid Tissue - immunology / Memory B cells / Memory B Cells - immunology / Memory cells / Microbiota / multidisciplinary / Palatine Tonsil - immunology / Plasma / Population / Science / Science (multidisciplinary) / Small intestine / Somatic hypermutation / Somatic hypermutation (SHM) / Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism