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
- Author(s): Walsh, Nicole Corinne;
- Advisor(s): Teitell, Michael A;
- et al.
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.