| 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-kappaB 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. |
