Year: 1991
Type: review
Abstract: In the 1940s, anti-IgG autoantibodies were discovered in the sera of patients with rheumatoid arthritis and given the term rheumatoid factors (RF).'The measurement of agglutinating IgM-RF is still the most useful serological test for the diagnosis of rheumatoid arthritis.High titers of IgM-RF are also present in primary Sjogren's syndrome, mixed cryoglobulinemia, and in several different chronic infections (1).Recent advances in molecular and cellular immunology are gradually revealing the genetic and environmental factors that control RF production.Two sets of results were largely unex- pected.First, genes encoding RF are present in most normal people, and their expression is carefully regulated during the development of the immune system.Second, lymphocytes with RF receptors on their plasma membranes are remarkably abundant in normal people, who have only low levels ofcircu- lating autoantibody.These data have suggested a new role for RF in the capture, processing, and presentation to T cells of antigens trapped in immune complexes.They may explain why RF production is vestained in patients with both rheuma- toid arthritis and lymphoproliferative diseases. Genetics ofRFThe antibody molecule is composed of heavy and light chains that are encoded by genes on separate chromosomes.Aside from the diversity allowed by the pairing oftwo separate chains to form a heterodimer, each chain has a variable region capable of achieving tremendous diversity through the process of im- munoglobulin gene arrangement.The haploid human genome contains -100-200 heavy chain variable (V) region genes, -100 kappa light chain V genes, and an unknown number oflambda light chain V genes (2, 3).A functional light chain immunoglobulin gene is gener- ated by the rearrangement in early B lymphocytes of one V gene to a separate joining (J) gene segment.In the case of the heavy chain gene, an additional gene segment, termed D for diversity, rearranges with the J segment before V gene rear- rangement.This process, together with inaccuracies produced during VDJ and VJ recombination, and sequential somatic mutations in antibody V genes, produces a virtually unlimited array of different antibody molecules.Because immunoglobu- Receivedfor
DOI: 10.1172/jci115007
Authors: D A Carson, P P Chen, T J Kipps
Institution: University of California San Diego
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1971392253