Murine γδ T Cells Render B Cells Refractory to Commitment of IgA Isotype Switching

γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ⁻/⁻) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ⁻/⁻ mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells. Likewise, the TCRδ⁻/⁻ mice produced much higher levels of serum IgA isotype. Here, surface IgA expression and number of IgA secreting cells were also elevated in the culture of spleen and bone marrow (BM) B cells. Germ-line α transcript, an indicator of IgA class switch recombination, higher in PP and MLN B cells from TCRδ⁻/⁻ mice, while it was not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was much higher in the spleen from TCRδ⁻/⁻ mice. These results suggest that γδ T cells control the early phase of B cells, in order to prevent unnecessary IgA isotype switching. Furthermore, this regulatory role of γδ T cells had lasting effects on the long-lived IgA-producing plasma cells in the BM.

Expression of IgA class switching gene in tonsillar mononuclear cells in patients with IgA nephropathy / 中华肾脏病杂志

Objec0tive To investigate the molecular mechanism of the mal-production of IgA and IgA1 by tonsillar mononuclear cells (TMCs) in IgA nephropathy (IgAN) patients by measuring the mRNA expression of Iα-Cα germline transcript and the mRNA and protein expression of activated induced cytidine deaminase (AID) in cultured TMCs stimulated with lipopolysaccharide (LPS) or hemolytic streptococcus (HS) in IgAN patients as well as the chronic tonsilitis patients. Methods Twent-seven IgAN patients admitted into our hospital from Jan.2009 to Feb.2010 were enrolled.Twent-seven patients with chronic tonsillitis without renal disease were selected as control.Tonsillar mononuclear cells were isolated by density gradient centrifugation in lymphocyte separation medium.The amount of IgA or IgA1 secreted in the culture supernatants was determined by specific enzyme-linked immunosorbent assay (ELISA).Expressions of Iα-Cα germline transcript and AID mRNA were examined by real-time PCR.The AID protein was determined by Western blot. Results The production of IgA and IgA1 protein,especially the ratio of IgA1/IgA and the expression of AID protein in TMCs were significantly increased in IgAN group compared with chronic tonsillitis group (all P＜0.05).The IgA and IgA1 level of stimulated TMCs were obviously increased in patients with IgAN compared with control group (P＜0.05).And the expressions of Iα-Cα mRNA,AID mRNA and AID protein were up-regulated significantly in stimulated TMCs (all P＜0.05). Conclusions Both LPS and HS can induce the production of IgA and IgA1 and up-regulate the expressions of AID and Iα-Cα in TMCs of IgAN patients.Our results indicate that the TMCs are capable of producing high level of IgA and IgA1 stimulated by LPS or HS,whuch may be due to the　 incression of AID and Iα-Cα.