Regulatory aspects of clonally expanded B-1 (CD5+ B) cells.
B-1 (CD5+ B) cells appear early in ontogeny, produce mainly unmutated polyreactive antibodies, and are capable of self-renewal. B-1 cells clonally expand with age and are the malignant cell in chronic lymphocytic leukemia. In this report immunological analysis of B-1 malignancies in NZB mice, a murine model of chronic lymphocytic leukemia, is related to current information on B-1 cells. B-1 clones from NZB mice produce high levels of interleukin-10, detected at the RNA level by semi-quantitative polymerase chain reaction. In addition, the B-1 malignant clones in NZB mice and their hybrids, are negative for B220/6B2 expression, the B-specific antigenic form of CD45 which is a membrane-associated phosphatase involved in lymphocyte activation. Both the autocrine production by B-1 cells of interleukin-10 and altered CD45 expression may be responsible for the clonal expansion of these cells, as well as the accompanying T cell expansion. We report the establishment of an in vitro cytotoxic CD8+ T cell line derived from an NZB with a B-1 malignancy. The effect of B-1 cell-derived interleukin-10 on subsets of T lymphocytes may account for the immunoregulatory properties of B-1 cells. In addition, the NZB malignancies were also characterized for immunoglobulin variable region sequence and antigen specificity. The B-1 malignancies produced immunoglobulin derived from unmutated germline sequences with no N base substitutions. It appears that both the immunoglobulin and interleukin-10 produced by the B-1 malignant cell in NZB mice may have immunoregulatory properties. A study of B-1 malignancies may shed light on the immunoregulatory properties of non-clonally expanded normal B-1 cells.
Raveché
E S
ES
Department of Pathology, UMDNJ, New Jersey Medical School, Newark 07103.
Phillips
J
J
Mahboudi
F
F
Dang
A
A
Fernandes
H
H
Ramachandra
S
S
Lin
T
T
Peng
B
B
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015152:Blotting, Northern; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000502:physiology; D004247:DNA / Q000032:analysis; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000032:analysis; D007958:Leukocyte Count; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D015703:Antigens, CD; D016207:Cytokines; D007136:Immunoglobulins; D004247:DNA; D017493:Leukocyte Common Antigens