Abstract
SummaryPKCβ-null (Prkcb−/−) mice are severely immunodeficient. Here we show that mice whose B cells lack PKCβ failed to form germinal centers and plasma cells, which undermined affinity maturation and antibody production in response to immunization. Moreover, these mice failed to develop plasma cells in response to viral infection. At the cellular level, we have shown that Prkcb−/− B cells exhibited defective antigen polarization and mTORC1 signaling. While altered antigen polarization impaired antigen presentation and likely restricted the potential of GC development, defective mTORC1 signaling impaired metabolic reprogramming, mitochondrial remodeling, and heme biosynthesis in these cells, which altogether overwhelmingly opposed plasma cell differentiation. Taken together, our study reveals mechanistic insights into the function of PKCβ as a key regulator of B cell polarity and metabolic reprogramming that instructs B cell fate.
Highlights
B cells are key components of adaptive immunity that provide systemic defense against pathogenic infections through the production of highly specific antibodies
PKCb Promotes Germinal Center Formation and Plasma Cell Differentiation While PrkcbÀ/À mice exhibit severe immunodeficiency in response to T cell-dependent antigens (Leitges et al, 1996), it is unclear whether B cells contribute to the severe phenotype in these mice
We challenged WT and PrkcbÀ/À chimeras with NP23 conjugated to keyhole limpet haemocyanin (KLH) and Alum via intra-peritoneal injection and analyzed the immune response in the spleen at day 13 (Figures 1A–1G)
Summary
B cells are key components of adaptive immunity that provide systemic defense against pathogenic infections through the production of highly specific antibodies. The internalized antigen is presented as cell surface peptides on class II major histocompatibility complex molecules (MHC-II) (Batista and Harwood, 2009), resulting in the engagement of specific CD4+ helper T cells and providing a second signal for maximal B cell activation. B cells in the GC shuttle between the light and the dark zone and BCRs with high antigen affinity are iteratively selected. These B cells exit the GC and differentiate into either high-affinity antibody secreting long-lived plasma cells or temporarily quiescent memory cells that can undergo plasma cell differentiation upon re-encountering the same antigen (McHeyzer-Williams and McHeyzer-Williams, 2005)
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