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bioRxiv · 10.1101/332361

Absence of surface IgD does not impair naive B cell homeostasis and memory B cell formation in humans

Nechvatalova, J.·Bartol, S. J. W.·Chovancova, Z.·Boon, L.·Vlkova, M.·van Zelm, M. C.
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Abstract

One Sentence SummaryHuman B cells with a genetic defect in IGHD develop normally in vivo, and do not have a competitive disadvantage to IgD-expressing B cells for developing into memory B cells.\n\nAbstractSurface immunoglobulin D (IgD) is co-expressed with IgM on naive mature B cells. Still, the role of surface IgD remains enigmatic even 50 years after its initial discovery. We here examined the in vivo role of surface IgD in human B-cell homeostasis and antibody responses in four individuals with heterozygous nonsense mutations in IGHD. All IGHD heterozygous individuals had normal numbers of B cells and serum immunoglobulins, and did not show signs of immunodeficiency or immune dysregulation. IgD+ and IgD- naive mature B cells were present in equal numbers and showed similar immunophenotypes, except for decreased expression of CD79b in the IgD- subset. Furthermore, both IgD+ and IgD- naive mature B cells had normal replication histories, similar capacities to differentiate into plasma cells upon in vitro stimulation, and Ig switched memory B cells showed similar levels of somatic hypermutations. Thus human B cells lacking IgD expression develop normally and generate immunological memory in vivo, suggesting that surface IgD might function more restricted in regulating of B-cell activation to specific antigenic structures.

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Nechvatalova, J., Bartol, S. J. W., Chovancova, Z., Boon, L., Vlkova, M., van Zelm, M. C.. 2018-05-28. Absence of surface IgD does not impair naive B cell homeostasis and memory B cell formation in humans. https://doi.org/10.1101/332361

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