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.
Original language | English |
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Pages (from-to) | 668-682 |
Number of pages | 15 |
Journal | Mucosal immunology |
Volume | 15 |
Issue number | 4 |
Early online date | 28 Mar 2022 |
DOIs | |
Publication status | Published - Apr 2022 |
Bibliographical note
Funding:Open Access funding enabled and organized by Projekt DEAL. This work was, in part, funded by the Deutsche Forschungsgemeinschaft (DFG) through grant TRR130 (project P09) to H.M.J. and W.S., TRR130 (project P03) to D.M., TRR130 (project TP17 and C01) and Einstein Stiftung Berlin (A-2019-559) to A.E.H., DFG HU 1294/8-1 to A.H., as well as DFG GRK1660 to H.M.J., and BBSRC funding to A.F.C.
Copyright:
© 2022. The Author(s).
Keywords
- Animals
- Flagellin
- Immunoglobulin A/metabolism
- Intestinal Mucosa
- Kruppel-Like Transcription Factors/genetics
- Mice
- Peyer's Patches
- Plasma Cells