PKCb-null (Prkcb-/-) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCb fail to develop germinal centers and plasma cells, which in concert undermine affinity maturation and antibody production in response to immunization. Moreover, Prkcb-/- B cells fail to differentiate into plasma cells in response to viral infection. At a cellular level, we show that activated Prkcb-/- B cells exhibit defective antigen polarization and mTORC1 signaling. While the loss of antigen polarization impairs antigen presentation and restricts the potential of Prkcb-/- B cells to develop into GC B cells, altered mTORC1 signaling affects gene expression, metabolic reprogramming and mitochondrial remodeling which together overwhelmingly oppose commitment to plasma cell differentiation. Mechanistically, we show that PKCb-mediated metabolic reprogramming is required for sustained heme biosynthesis that is essential for effector fate decision in B cells. Taken together, our study reveals mechanistic insights into the function of PKCb as a key regulator of B-cell polarity and metabolic reprogramming that instructs B-cell fate. SOURCE: Carlson Tsui (carlson.tsui@crick.ac.uk) -  The Francis Crick Institute

Pluto Bioinformatics

GSE111702: The role of PKC-beta in B cell activation