The accumulative and maturative type of B-cell activation in synovitis: a new concept of B-cell activation in autoimmune diseases
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KeywordsRheumatoid Arthritis Synovitis Maturative Type Germinal Centre Histological Pattern
B-cells and plasma cells in chronic synovitis of osteoarthritis (OA), reactive arthritis (ReA) and rheumatoid arthritis (RA) show two different histological patterns: lymphoplasmacellular pattern and germinal centre (GC) pattern. To clarify what immunological mechanisms stands beyond these histological patterns, IgVh gene analysis from the B and plasma cells present in those patterns was performed.
IgVh gene repertoires were determined from RNA (OA = 5, ReA = 2, RA = 5), prepared from tissue cryosections and from isolated B-cells and plasma cells (plc) by micromanipulation. The B-cell environment was analysed immunohistochemically by detecting plc (IgM, IgG, IgA), B-lymphocytes (CD20) and Ki-67 positive (proliferating) cells.
In the lymphoplasmacellular pattern of OA (n = 5), somatically highly mutated IgVh genes (R/S: CDR=R/S = 5.3; Fr=R/S = 2.0) could be detected, but no clonal relation could be established amongst them. The plc of the GC pattern in ReA (n = 2) and RA (n = 5) revealed highly somatically mutated IgVh genes: R/S: CDr=R/S = 3.4; Fr=R/S = 1.7; and CD20+ B cells in germline configuration. A clonal relation between low mutated B cells and highly mutated plc could be established indicating a local clonal expansion. A proliferation of CD20+ B cells could only be observed in GC.
Therefore, two different patterns of B-cell activation may be defined: (1)The accumulative type: already activated B cells migrate into the synovial tissue and accumulate there without further IgVh diversification. (2)The maturative type of B-cell proliferation with IgVh diversification occurring in a GC like reaction. The two different patterns of B-cell activation may reflect that different antigens are involved in autoimmune and degenerative diseases. Since in organ specific autoimmune diseases (RA, Morbus Sjögren, Morbus Basedow) a local germinal centre reaction takes place, it is likely that the B cells are expanded by disease specific antigens. The experimental expression of IgVh genes isolated from these germinal centre B cells may therefore lead to the identification of pathogenic organ specific antigens.