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Kindlin‐3 maintains marginal zone B cells but confines follicular B cell activation and differentiation.
- Source :
- Journal of Leukocyte Biology; Apr2022, Vol. 111 Issue 4, p745-758, 14p
- Publication Year :
- 2022
-
Abstract
- Integrin‐mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin‐3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell‐specific Kindlin‐3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell‐specific Kindlin‐3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin‐3 knockout B cells VLA‐4 as well as LFA‐1‐mediated adhesion was abrogated, and short‐term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin‐3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin‐3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch. [ABSTRACT FROM AUTHOR]
- Subjects :
- B cell differentiation
B cells
BONE marrow cells
GERMINAL centers
KNOCKOUT mice
Subjects
Details
- Language :
- English
- ISSN :
- 07415400
- Volume :
- 111
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Journal of Leukocyte Biology
- Publication Type :
- Academic Journal
- Accession number :
- 155950028
- Full Text :
- https://doi.org/10.1002/JLB.1HI0621-313R