B cell–intrinsic requirement for STK4 in humoral immunity in mice and human subjects

To the Editor: Biallelic loss-of-function mutations in serine-threonine kinase 4 (STK4), also known as mammalian sterile 20-like 1 (MST1), are associated with a combined immunodeficiency characterized by recurrent bacterial, fungal, and viral infections.1-6 Most patients have intermittent neutropenia, T and B lymphopenia, and, paradoxically, specific antibody defects despite the reported presence of increased levels of serum IgG, IgA, and IgE antibodies and antibody-mediated autoimmune cytopenias.1-6 Although there have been numerous studies of neutrophil, macrophage, dendritic cell, and T-cell function in Stk4 knockout mice,7-9,E1,E2 the nature and basis of the underlying B-cell dysregulation in STK4-deficient patients remains poorly characterized. [...]there were no differences in B-cell receptor–mediated upregulation of CD69 and CD86 after in vitro stimulation with cognate antigen of STK4-deficient mouse B cells (Fig 2, D). Interestingly, despite the impaired specific antibody secretion in mice with Stk4Y88del/Y88del B cells, STK4 deficiency did not quantitatively affect the ability of these SWHEL B cells to generate plasma cells in vivo (Fig 2, I-K). [...]similar to B cells from STK4-deficient patients, Stk4Y88del/Y88del B cells are able to differentiate into plasma cells, but these plasma cells do not secrete adequate amounts of specific antibody.