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Forschungsdatenbank PMU-SQQUID

Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation
Harzschel, A; Li, LX; Krenn, PW; Szenes-Nagy, E; Andrieux, G; Bayer, E; Pfeifer, D; Polcik, L; Denk, U; Hopner, JP; Karabatak, E; Danner, DJ; Tangermann, S; Kenner, L; Jumaa, H; Greil, R; Borries, M; Ruppert, R; Maity, PC; Hartmann, TN
Originalarbeiten (Zeitschrift)


Bayer Elisabeth
Denk Ursula
Greil Richard


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.

Find related publications in this database (Keywords)

B cell activation
follicular B cells
Integrin adhesion
marginal zone B cells