Salivary gland lymphomas in patients with Sjögren's syndrome may frequently develop from rheumatoid factor B cells.
OBJECTIVE
Patients with Sjögren's syndrome (SS) have an increased risk of developing monoclonal B cell non-Hodgkin's lymphomas (MNHL), which frequently occur in the salivary glands (SG). The transition from the benign lymphocyte infiltrate of the gland that characterizes SS to MNHL is not well understood. Previous sequence analyses of the expressed variable (V) region genes have supported the theory that the surface Ig (sIg) plays an important role in the initial expansion of nonmalignant B cell clones and in lymphomagenesis. However, the antigenic specificities of these B cells were unknown. We describe the specificities of the Ig expressed by 2 cases of MNHL that developed in the SG of 2 patients with SS.


METHODS
The expressed V genes were amplified by polymerase chain reaction from biopsy specimens, sequenced, and subcloned into eukaryotic expression vectors. The constructs were transfected into P3X63-Ag8.653 cells to obtain 2 monoclonal cell lines, each secreting 1 of the sIg expressed by the MNHL. These IgM were tested by enzyme-linked immunosorbent assay and immunofluorescence against a panel of antigens potentially implicated in SS.


RESULTS
Our main finding was that the Ig products of the neoplastic B cells were rheumatoid factors (RF). Contrary to expectations, they did not react with nuclear or cytoplasmic antigens, double-stranded DNA, self antigens commonly bound by natural autoantibodies, or SG tissue.


CONCLUSIONS
Previous analyses of V gene use have provided indirect evidence that SG MNHL may frequently express RF. We demonstrate that this hypothesis is true in the 2 patients we studied. Large-scale studies will be needed to establish the exact frequency of RF specificity among SS-associated MNHL.
Martin
T
T
Université Louis Pasteur, Strasbourg, France.
Weber
J C
JC
Levallois
H
H
Labouret
N
N
Soley
A
A
Koenig
S
S
Korganow
A S
AS
Pasquali
J L
JL
D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology; D005260:Female; D005784:Gene Amplification; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000150:complications / Q000235:genetics / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics / Q000276:immunology; D008297:Male; D009154:Mutation; D012217:Rheumatoid Factor / Q000096:biosynthesis* / Q000097:blood; D012468:Salivary Gland Neoplasms / Q000150:complications*; D012859:Sjogren's Syndrome / Q000150:complications*
D001324:Autoantigens; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D012217:Rheumatoid Factor