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Liver Kinase B1 Controls T Follicular Helper Cell Differentiation and Germinal Center Formation through Regulation of Nuclear Factor kappa-light-chain-enhancer of Activated B cells


Germinal centers (GCs) are a key feature during a T-dependent immune response. Mature B

cells in secondary lymphoid organs, such as the spleen and lymph nodes, remain quiescent

until they encounter foreign antigen. Antigen activated B cells that receive co-stimulation from

cognate T cells form germinal centers. GC B cells undergo rapid proliferation and programmed

DNA damage of the immunoglobulin genes (IG) that modifies the B cell receptor to increase its

affinity to the activating antigen. B cells that successfully rearrange their B cell receptors exit

the germinal center as long-lived, antibody secreting plasma cells or memory B cells. These

terminally differentiated cells are the basis of long-term immunity.

We previously discovered a pathway involved at the end of the germinal center reaction

important for plasma cell development involving Lkb1. To further investigate Lkb1's role in B

cell biology, we knocked Lkb1 out specifically in B cells. Unexpectedly, loss of Lkb1 in B cells

resulted in an increase of transitional B cells and a mixture of Lkb1+ and Lkb1- mature B cells.

Lkb1- B cells aberrantly secreted IL-6 due to activation of NF-κB signaling. B cell derived IL-6

contributes to generation of an activated environment, inducing T cell activation and the

differentiation of TFH cells. This activated environment spurred by loss of Lkb1 in a subset of B

cells ultimately resulted in spontaneous GC formation. Our results suggest an interesting new

role for Lkb1 in B cells as an essential negative regulator of activation.

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