ERK phosphorylation is RAF independent in naïve and activated B cells but RAF dependent in plasma cell differentiation
Laura Scheffler, Samantha Feicht, Tea Babushku, Laura B. Kuhn, Stefanie Ehrenberg, Samantha Frankenberger, F. Lehmann, Elias Hobeika, Berit Jungnickel, Manuela Baccarini, Georg W. Bornkamm, Lothar J. Strobl, Ursula Zimber‐Strobl
Abstract
, or both, we showed that Raf-1 and B-Raf acted together in mediating the positive selection of pre-B and transitional B cells as well as in initiating plasma cell differentiation. However, genetic or chemical inactivation of RAFs led to increased ERK phosphorylation in mature B cells. ERK activation in the absence of Raf-1 and B-Raf was mediated by multiple RAF-independent pathways, with phosphoinositide 3-kinase (PI3K) playing an important role. Furthermore, we found that ERK phosphorylation strongly increased during the transition from activated B cells to pre-plasmablasts. This increase in ERK phosphorylation did not occur in B cells lacking both Raf-1 and B-Raf, which most likely explains the partial block of plasma cell differentiation in mice lacking both RAFs. Collectively, our data indicate that B-Raf and Raf-1 are not necessary to mediate ERK phosphorylation in naïve or activated B cells but are essential for mediating the marked increase in ERK phosphorylation during the transition from activated B cells to pre-plasmablasts.