Anti-PRKCB (aa 631-642) polyclonal antibody

PKC beta-null (Prkcb(-/-)) mice are severely immunodeficient. Here we show that mice whose B cells lack PKC beta 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 PKC beta as a key regulator of B cell polarity and metabolic reprogramming that instructs B cell fate.

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD) on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein) or LPD (9% casein) for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03) and increased male offspring weight (P = 0.009) were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P < 0.02). However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg) and elevated heart rate (P < 0.05), whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk), LPD males had elevated adiposity (P = 0.04), reduced heart-to-body weight ratio (P = 0.04), and elevated circulating TNF-alpha levels (P = 0.015) compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb) and metabolism (Fto) in LPD offspring (P < 0.03). These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.