Analysis of the V kappa III variable regions of polyclonal rheumatoid factors arising during Epstein Barr virus induced infectious mononucleosis.
The mechanisms that govern autoantibody production are still under debate. In particular, auto-antibodies can appear as a consequence of a polyclonal activation of B cells or as a consequence of an antigen driven B cell expansion. The molecular analysis of the variable regions of auto-antibodies arising during different clinical situations can help to understand the origin of auto-antibodies. We recently described the main light chain variable regions of polyclonal rheumatoid factors occurring during rheumatoid arthritis and suggested that the mutation pattern of these regions could reflect an antigen driven process. Using the same approach, we now report the molecular analysis of the same light chain variable region containing a VKIII segment of rheumatoid factors originating from a polyclonal activation of B cells during an in vivo Epstein-Barr virus infection, infectious mononucleosis. The cDNA derived from rheumatoid factor synthetizing cells were amplified by two sets of polymerase chain reaction. The amplified products were cloned in M13mp19 phages and sequenced. The nucleotide analysis of the VKIII containing VK regions shows that: 1) the rheumatoid factor activity is associated with the 3 VKIII genes (Kv 325, Kv 328 and Vg) already known to encode for monoclonal and polyclonal rheumatoid factors, 2) there is a preferential use of Kv 328 and Vg, each one of these genes being poorly mutated, 3) the CDR mutation rates of these genes is no higher than the framework mutation rates, 4) there is a restriction of the JK usage; Kv 328 derived gene segments rearrange exclusively with JK1, Vg preferentially rearranges with JK1 and JK4. These results mainly suggest that naturally occurring polyclonal activation of autoreactive B cells produces poorly mutated autoantibodies.
Weber
J C
JC
Laboratoire d'Immunopathologie, Hôpitaux Universitaires de Strasbourg, Hôpital Civil, France.
Martin
T
T
Knapp
A M
AM
Pasquali
J L
JL
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002469:Cell Separation; D005434:Flow Cytometry; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000032:analysis* / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000032:analysis* / Q000235:genetics; D007244:Infectious Mononucleosis / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000737:chemistry* / Q000235:genetics
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D012217:Rheumatoid Factor