Bone marrow origin of a B-cell lymphoma.
To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre-B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre-neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.
Bertoli
L F
LF
Division of Developmental and Clinical Immunology, University of Alabama, Birmingham 35294.
Kubagawa
H
H
Borzillo
G V
GV
Burrows
P D
PD
Schreeder
M T
MT
Carroll
A J
AJ
Cooper
M D
MD
D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008223:Lymphoma / Q000145:classification / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009693:Nucleic Acid Hybridization; D010641:Phenotype
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; C044203:anti-IgM