Human rheumatoid B-1a (CD5+ B) cells make somatically hypermutated high affinity IgM rheumatoid factors.

摘要: To analyze the structure and formally ascertain B-1a cellular origin of IgM rheumatoid factor (RF) autoantibodies, we generated 4 RF mAb-producing cell lines using sorted (surface CD5+) cells from a patient with active arthritis. The mAb111, mAb112, mAb113, mAb114 were monoreactive displayed relatively high affinity for human IgG Fc fragment (Kd, 3.1 x 10(-7) to 6.8 M). lymphocytes that gave rise was confirmed by expression surface CD5 specific mRNA all lines. Analysis genes encoding mAb VH VL regions revealed members VHI VHIII families utilized in conjunction V kappa IIIa, IIIb, or lambda I genes. JH3 JH4 each twice. H chain CDR3 sequences divergent variable length. identical closely related those expressed "restricted" fetal B repertoire and/or JH-proximal. For instance, mAb111 gene likely constituted mutated variant 20P3 which is second most JH-proximal (125 kb JH). In addition, among have been found encode other RF, different antibodies induced exogenous Ag, natural autoantibodies adult neonatal repertoires. When compared known germline genes, number differences. By cloning sequencing DNA PMN same whose used generation, showed such differences resulted somatic hypermutation mAb112 gene. (112GL) presumably segment 51P1 distribution replacement silent mutation ratio nucleotide mutations highly consistent their selection Ag. mAb113 clonally as shown utilization sets VHI-D-JH4 IIIb-J displaying junctional sequences, presence two one mutations.(ABSTRACT TRUNCATED AT 400 WORDS)