Vasoactive intestinal peptide stimulates B cell maturation and class switch recombination 2257501

Abstract

Abstract Introduction Neuropeptides released from sensory neurons or neuroendocrine cells impact immune responses to pulmonary bacterial infection. We identified that in response to priming and infection with Streptococcus pneumoniae, pulmonary sensory neurons preferentially release vasoactive intestinal peptide (VIP), which stimulates IgG production. Methods To determine how vasoactive intestinal peptide (VIP) acts on antibody-secreting cells, we cultured naïve B cells with or without VIP in TLR or TLR+BCR stimulation media for 96 hours, sampling media and cells every 24 hours. Results In both media, VIP increased the number of isotype-switched (IgD-IgM-) differentiated and stimulated (Irf4+ Irf8+) B cells after 72 and 96 hours of culture. Additionally, the activation of these cells increased as Stat3 levels rose more with VIP. CD138+ Blimp+ plasma cells were increased with VIP, and the proportion of Stat3+ activated plasma cells was also increased. Isotyping analysis showed that IgG2a, IgG2b and IgG3 were consistently upregulated with VIP in both media after 96 hours. Finally, key enzymes involved in class switch recombination, AID, Rag1 and Rag2 were upregulated in both media with VIP. Conclusion The interrelated processes of B-cell maturation and class switch recombination are accelerated in the presence of VIP. This work is funded by NIH R01HL176463-01A1. Funding Source NIH/NHLBI Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)