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

• Published in: Journal of allergy and clinical immunology Vol. 143; no. 6; pp. 2302 - 2305
• Main Authors: Moran, Imogen, Avery, Danielle T., Payne, Kathryn, Lenthall, Helen, Davies, E. Graham, Burns, Siobhan, Ip, Winnie, Oleastro, Matÿfffedas M., Reisli, Ismail, Guner, Sukru, Keles, Sevgi, Notarangelo, Luigi, Deenick, Elissa K., Goodnow, Christopher C., Zahra, David, Brink, Robert, Wong, Melanie, Tangye, Stuart G., Ma, Cindy S., Phan, Tri Giang
• Format: Journal Article
• Language: English
• Published: St. Louis Elsevier Inc 01.06.2019; Elsevier Limited
• Subjects: Antigens; B-cell receptor; Bone marrow; CD69 antigen; CD86 antigen; Defects; Dendritic cells; Human subjects; Humoral immunity; Immunodeficiency; Immunoglobulin A; Immunoglobulin E; Immunoglobulin G; Immunoglobulins; Kinases; Ligands; Lymphocytes B; Lymphocytes T; Lymphopenia; Macrophages; Mutation; Neutropenia; Plasma cells; Protein-serine/threonine kinase
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2019.02.010

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.