Expression of multiple beta 1 integrins on circulating monoclonal B cells in patients with multiple myeloma.
We have previously reported the presence of monoclonal, tumor-related B lineage cells in the blood of myeloma patients. The cells are continuously differentiating, and the majority are at a very late stage of B cell differentiation into plasma cells, consistent with the hypothesis that they comprise a precursor cell subset responsible for disseminating and possibly for relapse of the disease. The pattern of beta 1 integrin expression on monoclonal B lineage cells from blood and bone marrow of myeloma patients was evaluated using multiparameter flow cytometry in comparison to normal blood or tissue B cells and malignant B cells from B-CLL, B lymphoma, or plasma cell leukemia. The alpha 4 and beta 1 chains were found on the majority of normal B cells, usually with a higher expression of alpha 4 compared to beta 1. alpha 5 was detectable at low density on B cells from lymph node, bone marrow, and lamina propria. the alpha 2 and alpha 6 chains are absent on B cells localized in normal lymphoid tissues as well as on normal blood B cells and in vitro activated B cells. In myeloma, the blood B cells express alpha 2, alpha 5, and alpha 6, suggesting important functional differences between these tumor-related B cells and their normal counterparts. The plasma cells located in myeloma bone marrow express no alpha 2, and almost no alpha 6, although they have variable expression of alpha 4, alpha 5, and beta 1. Thus the end-stage plasma cells appear to lack receptors that would support a propensity for invasion of basement membranes and exit to extravascular spaces. In contrast, the circulating plasmablasts in a patient with plasma cell leukemia make up a large subset of early plasma cells expressing all integrin receptors analyzed, including alpha 2 and alpha 6. Malignant cells from B-CLL and B lymphoma express only the alpha 4 and beta 1 integrins, and some B-CLL have very low levels of alpha 3, but no alpha 2, alpha 5, or alpha 6, suggesting that they may be limited to the vascular spaces and do not extravasate, at least for the stages of disease analyzed here.(ABSTRACT TRUNCATED AT 400 WORDS)
Jensen
G S
GS
Department of Immunology, University of Alberta, Edmonton, Canada.
Belch
A R
AR
Mant
M J
MJ
Ruether
B A
BA
Yacyshyn
B R
BR
Pilarski
L M
LM
D015703:Antigens, CD / Q000097:blood; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000097:blood; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000032:analysis* / Q000096:biosynthesis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology; D007952:Leukemia, Plasma Cell / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000097:blood / Q000276:immunology; D009101:Multiple Myeloma / Q000097:blood* / Q000276:immunology* / Q000473:pathology
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D016023:Integrins