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ABO-A antibody induction in mice is T cell-dependent, estrogen-independent, and modulated by CD22

  • Author(s) / Creator(s)
  • ABO antibodies pose barriers in transplantation but remain poorly studied. We investigated anti-A natural antibodies (nAbs) and induced antibodies (iAbs) in wild-type (WT), CD19KO, and CD22KO mice in the context of major histocompatibility complex-syngeneic or major histocompatibility complex-allogeneic stimulation by ABO-A blood cell membranes (BCM) from A-transgenic mice, or xenogeneic human (Hu-A) BCM. CD19KO mice failed to produce anti-A nAbs and iAbs. Syngeneic A-transgenic-BCM failed to stimulate anti-A iAbs in WT mice, in contrast to allogeneic A-transgenic-BCM and xenogeneic Hu-A-BCM. Hu-ABCM failed to stimulate anti-A iAbs in CD4-T cell-depleted or CD4KO mice, reversed with CD4-T cell reconstitution. Although anti-A nAbs were absent in estrogen-receptor-α-deficient mice, anti-A iAbs were easily stimulated. Anti-A nAbs were higher in CD22KO than in WT mice, with pubertal females producing higher levels than males. Anti-A iAbs were stimulated in CD22KO mice by syngeneic A-transgenic-BCM or by Hu-A-BCM after CD4T cell depletion. We conclude that anti-A nAbs and iAbs are produced by B1a-cells. In WT mice, stimulation of anti-A iAbs requires exposure to nonself A-antigen together with foreign proteins and is T cell dependent. Without CD22-mediated inhibition, anti-A iAb stimulation does not require foreign protein and is T cell-independent. Anti-A iAbs are estrogenindependent, whereas anti-A nAbs are estrogen-dependent and could be elicited by estrogen in males.

  • Date created
    2025-03-19
  • Subjects / Keywords
  • Type of Item
    Article (Published)
  • DOI
    https://doi.org/10.7939/r3-3qjn-6k34
  • License
    Attribution-NonCommercial 4.0 International