Krüppel-like factor 2 controls IgA plasma cell compartmentalization and IgA responses

Wittner J, Schulz S, Steinmetz T, Berges J, Hauke M, Channell WM, Cunningham AF, Hauser AE, Hutloff A, Mielenz D, Jäck HM, Schuh W (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Mucosal Immunology Nature Publishing Group: Open Access Hybrid Model Option A

DOI: 10.1038/s41385-022-00503-0

Abstract

Krüppel-like factor 2 (KLF2) is a potent regulator of lymphocyte differentiation, activation and migration. However, its functional role in adaptive and humoral immunity remains elusive. Therefore, by using mice with a B cell-specific deletion of KLF2, we investigated plasma cell differentiation and antibody responses. We revealed that the deletion of KLF2 resulted in perturbed IgA plasma cell compartmentalization, characterized by the absence of IgA plasma cells in the bone marrow, their reductions in the spleen, the blood and the lamina propria of the colon and the small intestine, concomitant with their accumulation and retention in mesenteric lymph nodes and Peyer’s patches. Most intriguingly, secretory IgA in the intestinal lumen was almost absent, dimeric serum IgA was drastically reduced and antigen-specific IgA responses to soluble Salmonella flagellin were blunted in KLF2-deficient mice. Perturbance of IgA plasma cell localization was caused by deregulation of CCR9, Integrin chains αM, α4, β7, and sphingosine-1-phosphate receptors. Hence, KLF2 not only orchestrates the localization of IgA plasma cells by fine-tuning chemokine receptors and adhesion molecules but also controls IgA responses to Salmonella flagellin.

Authors with CRIS profile

Jens Wittner Department of Molecular Immunology Sebastian Schulz Professur für Immunologie Tobit Steinmetz Professur für Immunologie Johannes Berges Department of Medicine 5 – Haematology and Oncology Dirk Mielenz Medizinische Fakultät Hans-Martin Jäck Department of Molecular Immunology Wolfgang Schuh Department of Molecular Immunology

Involved external institutions

University of Birmingham GB United Kingdom (GB) Charité - Universitätsmedizin Berlin DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE)

How to cite

APA:

Wittner, J., Schulz, S., Steinmetz, T., Berges, J., Hauke, M., Channell, W.M.,... Schuh, W. (2022). Krüppel-like factor 2 controls IgA plasma cell compartmentalization and IgA responses. Mucosal Immunology. https://doi.org/10.1038/s41385-022-00503-0

MLA:

Wittner, Jens, et al. "Krüppel-like factor 2 controls IgA plasma cell compartmentalization and IgA responses." Mucosal Immunology (2022).

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