T-cell clonal expansion in patients with B-cell lymphoproliferative disorders.
We investigated whether T-cell clonal expansion could be found in the blood of 14 untreated patients with B-cell lymphoproliferative disorders [5 B-chronic lymphocytic leukemia (CLL), 4 myelomas, 5 non-Hodgkin lymphoma (NHL)]. The putative presence of T-cell clonotypes was analyzed with a polymerase chain reaction-based method determining V-D-J junction size patterns in 24 T-cell receptor (TCR) V beta subfamilies. This high-resolution method, analyzing CDR3 sizes of TCR transcripts, was used in conjunction with cytometric analysis of the corresponding T-cell subpopulations with 18 TCR V beta-specific monoclonal antibody. We found multiple dominant T-cell clonotypes in the blood of most patients with B-CLL or myeloma as well of a patient with stage IV NHL. In some cases, T-cell clonal expansion was so dominant that the percentage of these clonal T-cell subpopulations in blood represented more than the mean +2 SD value determined in a series of healthy controls. We conclude that a systemic antigen-specific (i.e., leading to clonotypic expansion) immune reaction involving few TCR clonotypes is a hallmark of disseminated B-cell malignancies. The nature of the putative antigens recognized is not known presently. Nonetheless, such insights into the T-cell repertoire of these patients may help to reassess the potential of immunotherapeutic strategies in B-cell malignancies.
Alatrakchi
N
N
Laboratoire d'Immunologie Cellulaire, INSERM U3331, Villejuif, France.
Farace
F
F
Frau
E
E
Carde
P
P
Munck
J N
JN
Triebel
F
F
D000328:Adult; D000368:Aged; D022801:Complementarity Determining Regions; D004247:DNA / Q000032:analysis; D005260:Female; D019674:Genes, T-Cell Receptor beta / Q000235:genetics; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D022801:Complementarity Determining Regions; D007137:Immunoglobulin alpha-Chains; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA