RT Journal Article SR Electronic T1 Absence of surface IgD does not impair naive B cell homeostasis and memory B cell formation in humans JF bioRxiv FD Cold Spring Harbor Laboratory SP 332361 DO 10.1101/332361 A1 J. Nechvatalova A1 S.J.W. Bartol A1 Z. Chovancova A1 L. Boon A1 M. Vlkova A1 M.C. van Zelm YR 2018 UL http://biorxiv.org/content/early/2018/05/28/332361.abstract AB One Sentence Summary Human 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.Abstract Surface 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.