title: Increased dimeric IgA-producing B cells in tonsils in IgA nephropathy determined by in situ hybridization for J chain mRNA.
abstract: The origin of mesangial IgA deposits in IgA nephropathy (IgAN) remains obscure. A significant proportion of deposited immunoglobulin is dimeric (J chain-positive). Previous studies of J chain expression within lymphoid tissue in IgAN have utilized antibodies which other investigators have found to be non-specific. To address this problem, we have developed and in situ hybridization (ISH) method for the detection of J chain mRNA within IgA plasma cells. Tonsils from 12 patients with IgAN and 12 controls were studied using (i) non-isotopic ISH for J chain mRNA, and (ii) combined immunofluorescence (IF) and fluorescent ISH. J chain mRNA-positive cells were identified in germinal centres, and within the subepithelial and interfollicular zones. A greater number of J chain mRNA-positive cells were found in the germinal centres of patients (mean 57.7 +/- 4.6 cells/10(5) micron2) compared with controls (mean 36.9 +/- 3.5 cells/10(5) micron2) (P < 0.001). Combined IF and fluorescent ISH showed a greater proportion of J chain mRNA-positive interfollicular IgA cells in patient tonsils (32 +/- 3.4%) compared with controls (21 +/- 2.3%; P < 0.02). These results indicate a shift towards dimeric IgA production in the tonsils in IgAN. In addition, the finding of excess numbers of J chain-positive Iga-negative cells within germinal centres suggests that an abnormality may be present at the B cell differentiation stage before IgA switching. These results further highlight immune abnormalities within the tonsil as a central feature of abnormal polymeric IgA biology in this common form of glomerulonephritis.
authors.affiliation: Department of Nephrology, Leicester General Hospital, UK
authors.forename: S J
authors.initials: SJ
authors.lastname: Harper
authors.forename: A C
authors.initials: AC
authors.lastname: Allen
authors.forename: M C
authors.initials: MC
authors.lastname: Béné
authors.forename: J H
authors.initials: JH
authors.lastname: Pringle
authors.forename: G
authors.initials: G
authors.lastname: Faure
authors.forename: I
authors.initials: I
authors.lastname: Lauder
authors.forename: J
authors.initials: J
authors.lastname: Feehally
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007144:Immunoglobulin J-Chains / Q000032:analysis*; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D014066:Palatine Tonsil / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D007070:Immunoglobulin A; D007144:Immunoglobulin J-Chains; D012333:RNA, Messenger