Surface IgD is coexpressed with IgM on naive mature B cells. Still, the role of surface IgD remains enigmatic even 50 y after its initial discovery. In this study, we examined the in vivo role of surface IgD in human B cell homeostasis and Ab responses in four individuals with heterozygous nonsense mutations in IGHD All IGHD heterozygous individuals had normal numbers of B cells and serum Igs 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 and similar capacities to differentiate into plasma cells upon in vitro stimulation, and Ig class-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 restrictedly in regulating of B cell activation to specific antigenic structures.

Bioceros 3584CM Utrecht the Netherlands

Department of Clinical Immunology and Allergology St Anne's University Hospital in Brno 65691 Brno the Czech Republic Faculty of Medicine Masaryk University 62500 Brno the Czech Republic

Department of Immunology and Pathology Central Clinical School Monash University and The Alfred Hospital Melbourne Victoria 3004 Australia

Department of Immunology Erasmus MC University Medical Center 3015CN Rotterdam the Netherlands

References provided by Crossref.org