The Homeostasis of IgM Secreting Cells in Skin and Lymphoid Tissues and the Role of Secreted IgM in Modulating Il-10+ B Cells
Abstract
Immunoregulation is essential to restrain immune responses in infection, cancer, and inflammation; however, the signals governing the development and maintenance of two B lineage cells, IgM antibody secreting cells and IL-10+ B cells, are not fully understood. In this study, we used mice and human tissues to investigate antibody secreting cells in the skin, a significant site for immunoregulation. Antibody secreting cells reside in healthy mouse and human skin and develop independent of microbes or T cells. IgM is the predominant isotype produced in naïve mice. Chronic inflammation promotes the accumulation of IgM-secreting cells in the skin, and their survival is completely dependent on BAFF or APRIL. We also reveal secreted IgM (sIgM) as a novel regulator of IL-10+ B cell development. IL-10+ B cells expand in mice lacking sIgM (sIgM–/–) up to 10-fold relative to wildtype (WT) among all major B cell and Breg subsets. The IL-10+ B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10+ B cells. Lack of the high affinity receptor for sIgM, FcmR, in B cells translates into an intermediate IL-10+ B cell phenotype relative to WT or sIgM–/– mice. Our study shows that sIgM partially regulates IL-10 programming in B cells via B cell-expressed FcmR, thereby revealing a function of sIgM in regulating immune homeostasis.These findings reveal signals that govern the development of two immunoregulatory cell populations. Our results are of general B cell developmental interest as the relationship between sIgM and IL-10 has not been described previously. Additionally, these findings provide a new axis to modulate immune tolerance via manipulating IL-10+ B cells in different diseases by targeting either survival or expansion of IgM secreting cells or sIgM-FcmR signaling pathways. These pathways are of particular interest in the skin, where IL-10+ B cells and antibody-mediated diseases can be targeted locally via cutaneous treatments.
Subject Area
Immunology|Cellular biology|Microbiology
Recommended Citation
McGettigan, Shannon Eileen, "The Homeostasis of IgM Secreting Cells in Skin and Lymphoid Tissues and the Role of Secreted IgM in Modulating Il-10+ B Cells" (2024). ProQuest ETD Collection - Thomas Jefferson University. AAI31142704.
https://jdc.jefferson.edu/dissertations/AAI31142704
