Nuclear Receptors, Ligands and the Mammalian B Cell

Abstract

Questions concerning the influences of nuclear receptors and their ligands on mammalian B cells are vast in number. Here, we briefly review the effects of nuclear receptor ligands, including estrogen and vitamins, on immunoglobulin production and protection from infectious diseases. We describe nuclear receptor interactions with the B cell genome and the potential mechanisms of gene regulation. Attention to the nuclear receptor/ligand regulation of B cell function may help optimize B cell responses, improve pathogen clearance, and prevent damaging responses toward inert- and self-antigens.

How Estrogen, Testosterone, and Sex Differences Influence Serum Immunoglobulin Isotype Patterns in Mice and Humans

“…A potential ERE (rryyrnnntganc) is positioned between 5′Iγ2b and the Sγ2b switch site. Data from previously described chromatin immunoprecipitation (ChIP) experiments are shown [ 17 , 43 , 46 , 47 ]. These were from LPS-stimulated, purified C57BL/6 mouse B cells that were harvested after a one-day culture.…”

“…CA repeats are reminiscent of heptamer/nonamer sites important for V-D-J joining, and donor/acceptor sites central to RNA splicing and intron excision [ 39 , 40 , 41 , 42 ]. ERE appear in human and mouse S sites and regulatory regions [ 17 , 43 , 44 , 45 , 46 , 47 ]. Positions of ER binding are coincident with those of other factors such as Mediator and Ikaros [ 35 , 48 ], known contributors to enhanceosome/switchosome activity in the locus [ 17 ].…”

“…Positions of ER binding are coincident with those of other factors such as Mediator and Ikaros [ 35 , 48 ], known contributors to enhanceosome/switchosome activity in the locus [ 17 ]. ER and RNA Pol II exhibit coordinated binding, suggesting that ER may serve as an escort for RNA Pol II, which in turn supports sterile transcription and AID recruitment to initiate and modulate CSR [ 17 , 43 , 44 , 46 , 47 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Functional associations between polymorphic regions of the human 3′IgH locus and COVID-19 disease

“…We hypothesize that age and gender-associated differences in Sars-COV-2 infection could be explained by the presence of the consensus for the ERα lying in two copies in the polymorphic allele *2 of hs1.2 enhancer, and by the SNPs of the 3’RR1 palindrome. In several previous experiments, the immunomodulatory action of the 3’RR was confirmed on mouse B lymphocytes during the class switch recombination as well as during B cell maturation ( Jones et al, 20192019 , Jones et al, 2020 ). Additionally, in humans, several genomic variants located in the internal enhancers of the 3’RR1 have been reported to be associated to several immune-disorders and disease status ( Cianci et al, 2008 ).…”

Correlation of serum vitamin D concentration with humoral‐specific IgG2 and IgG4 levels in high responders to immunotherapy with a 300 IR sublingual house dust mite tablet

“…14 Indeed, correlations were described between serum vitamin A and IgG4 (as well as IgA), on the one hand, and between serum vitamin D and IgG3 (as well as IgM), on the other hand. 14 To our knowledge, however, no correlation was described between serum vitamin D and IgG4 or IgG2. On this basis, the significant correlations specifically observed in high responders between pretreatment levels of both vitamin D and specific IgG4 were not 1).…”