ANTIISLET CELL AND ANTIINSULIN ANTIBODY-PRODUCTION BY CD5- B-LYMPHOCYTES IN IDDM( AND CD5)

Citation
A. Munoz et al., ANTIISLET CELL AND ANTIINSULIN ANTIBODY-PRODUCTION BY CD5- B-LYMPHOCYTES IN IDDM( AND CD5), Diabetologia, 38(1), 1995, pp. 62-72
Citations number
63
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
0012-186X
Volume
38
Issue
1
Year of publication
1995
Pages
62 - 72
Database
ISI
SICI code
0012-186X(1995)38:1<62:ACAAAB>2.0.ZU;2-1
Abstract
Although CD5 + B lymphocytes are mostly committed to the production of polyreactive natural autoantibodies, CD5 + B lymphocytes committed to the production of somatically mutated and monoreactive high-affinity IgM autoantibodies have been also shown. Increased proportions of CD5 + B lymphocytes in some autoimmune diseases, including insulin-depende nt diabetes mellitus (IDDM), have been noticed. The present study was undertaken to analyse the differences between CD5+ and CD5- B lymphocy te subsets for production of IDDM-related autoantibodies, i. e. anti-h uman insulin antibodies (IA) and anti-human islet cell antibodies (ICA ). For this purpose, Epstein-Barr Virus(EBV)-transformation of FACS ce ll-sorted CD5+ and CD5- B lymphocytes and unfractionated enriched B ly mphocytes from nine IDDM patients treated exclusively with recombinant human insulin, and from four healthy control subjects was performed; a mean of 102-216 microcultures with a mean of 1,000-2,333 cells/micro culture for each B-lymphocyte fraction and individual was established. Data show that both CD5 + and CD5- B-lymphocyte subsets from either n ormal subjects or from IDDM patients receiving recombinant human insul in, contain B lymphocytes committed to the production of IA-IgM as a c ommon element of their repertoire. In contrast, cells committed to the production of IA-IgG were only detected among the CD5- B lymphocyte s ubset from some IDDM patients. Only one microculture, out of a total o f 6,211 screened (from control subjects and patients), in the CD5- B-c ell subset from a recently-diagnosed IDDM patient, was found to produc e ICA-IgM lambda. This might suggest that the frequency of circulating B lymphocytes committed to the production of ICA is very low even in IDDM patients bearing serum ICA. EBV-transformed B cells producing the ICA-IgM lambda were stabilized and cloned by somatic hybridization te chnique. This ICA-IgM lambda human monoclonal antibody, designated HY1 -MB91, is not polyreactive, but shows a restricted reactivity with hum an pancreatic islets, failing to react with other human tissues includ ing cerebellar cortex, and lacking rheumatoid factor and anti-DNA anti body activities. It also lacks reactivity with pancreatic islets from other mammalian species (rat, mouse and monkey) as well as with other rat tissues, including cerebellar cortex. The antigen recognized by HY 1-MB91 antibody in human islet cells is a cytoplasmic component mostly found in beta cells.