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The gammaherpesviruses (γHVs), human Kaposi sarcoma-associated herpesvirus (KSHV), EBV, and murine γHV68 are prevalent infections associated with lymphocyte pathologies. After primary infection, EBV and γHV68 undergo latent expansion in germinal center (GC) B cells and persists in memory cells. The GC reaction evolves and selects antigen-specific B cells for memory development but whether γHV passively transients or manipulates this process in vivo is unknown. Using the γHV68 infection model, we analyzed the Ig repertoire of infected and uninfected GC cells from individual mice. We found that infected cells displayed the hallmarks of affinity maturation, hypermutation, and isotype switching but underwent clonal expansion. Strikingly, infected cells displayed distinct repertoire, not found in uninfected cells, with recurrent utilization of certain Ig heavy V segments including Ighv10-1. In a manner observed with KSHV, γHV68 infected cells also displayed lambda light chain bias. Thus, γHV68 subverts GC selection to expand in a specific B cell subset during the process that develops long-lived immunologic memory.

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IntroductionNumerous hormones, neurotransmitters, and other stimuli exert their biological effect on cellular functioning through heptahelical receptors coupled to G proteins (GPCR – G protein-coupled receptors). Adrenergic receptors that belong to this superfamily of receptors are components of the sympathetic nervous system. They play a pivotal role in blood pressure regulation and myocardial contractility. Alterations of the adrenergic receptor pathway have been suggested to be involved in the pathophysiology of vasovagal syncope (VVS). The aim of the present study was to evaluate the distribution of Arg389Gly polymorphism within the ADRB1 gene among patients with recurrent syncope.Material and methodsArg389Gly single nucleotide polymorphism was analyzed in 205 patients with recurrent syncope. Ninety-five patients (46%) had a positive head-up tilt test (HUT) result. The control group comprised 143 non-fainting subjects. Genotyping was performed by restriction fragment length polymorphism (RFLP) with BstNI enzyme.ResultsBoth analyzed groups had similar distribution of the 389Gly allele. Sixty percent of polymorphic 389Gly carriers belong to the group of syncopal patients, while 40% belong to the control group of healthy subjects.ConclusionsAn association between syncopal incidence and Arg389Gly polymorphism within the ADRB1 gene was not found. The analyzed polymorphism affecting sympathetic activity does not influence vasovagal syncope in Polish patients.

The molecular mechanisms that regulate AID mutator activity at off-target genes are not well characterized. Mu et al. show AID phosphorylation dynamically controls activity at Myc and other sites. Pharmacological induction of AID phosphorylation leads to increased mutations, double strand breakss and translocations.