Increased mutations of CD72 transcript in B-lymphocytes from adolescent patients with systemic lupus erythematosus.
Recent studies have shown that B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE). Abnormal expression of molecules engaging in B-cell receptor (BCR) signaling and resultant hyperactivity of B cells has been reported in both mouse models of lupus and patients with SLE. CD72 on B cells is unique in that it regulates BCR signaling both positively and negatively. We analyzed the expression of CD72 protein and mRNA in peripheral blood B cells from adolescent patients with SLE. The expression level of CD72 on B cells of the patients was decreased compared with that on B cells of controls. Sequence analysis of CD72 mRNA showed significantly increased nucleotide mutations, including both nucleotide substitutions and deletions. Almost all (95.6%) of the CD72 transcripts from the patients had different nucleotide sequences from those of the wild type. About half (41.3%) of the mutations were point mutations located close to the sequence of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which negatively regulates BCR signaling. These results indicate that increased nucleotide mutation of CD72 mRNA accounts for the decreased expression level of CD72 in B cells, and it might be related to hyperactivity of B cells in patients with SLE.
Kaneko
Utako
U
Division of Pediatrics, Department of Homeostatic Regulation and Development, Niigata Graduate School of Medical and Dental Sciences, Niigata City, Japan. utako-k@jc5.so-net.ne.jp
Toyabe
Shin-ichi
S
Hara
Masanori
M
Uchiyama
Makoto
M
D000293:Adolescent; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C064228:CD72 protein, human; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell