H-2 control of expression of an idiotype shared by normal B cells and a B-cell lymphoma

Abstract

The spleens of normal B10.H-2aH-4bp/Wts (2a4b) mice contain cells which, in response to mitogen stimulation, secrete hemolytic antibody specific for a determinant present on both sheep and bromelain-treated mouse erythrocytes. These cells were found to be Ly-1 positive. Approximately 50% of these cells bear surface immunoglobulin (sIg) with the same idiotype as the sIg of a 2a4b-derived B-cell lymphoma, CH12. Backcross analysis revealed H-2 control of the frequency of the idiotype-positive B cell. The regulatory gene did not correlate with the Igh-1 allotype, and analysis of 22 inbred mouse strains mapped the gene to the I-E subregion. Surprisingly, only strains homozygous for Ek alpha expressed the idiotype, and expression was a recessive trait. Possible mechanisms for this control of idiotype expression and its relation to lymphomagenesis are discussed.

Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes.

“…At present, it is not possible to exclude either an antigen-or idiotypedriven clonal expansion. An idiotype-specific suppressor effect has been suggested for at least one of the idiotypes expressed by the PtC-specific Ly-1 + B cells (16), and selection of the PtC-specific repertoire by antiidiotype has been demonstrated (41) .…”

“…shown to bear the cell surface marker, Ly-1 (2,16), raising the possibility that anti-PtC is contained within the putatively restricted repertoire of Ly-1+ B cells .…”

The CH Series of Murine B Cell Lymphomas: Neoplastic Analogues of Ly‐1+ Normal B Cells

“…The reactive hapten can be exposed on various erythrocytes, including those of mice, by treatment with the proteolytic enzyme, bromelain. Cells which express immunoglobulin with this specificity can be found in the spleens of many (perhaps all) normal mice (Bishop & Haughton 1985), but their number is not increased by immunizing with SRBC. They include those cells which form "spontaneous" plaques on SRBC or bromelain-treated mouse erythrocytes (BrMRBC), or both.…”

“…When cells of the lymphoma, CHI2, are induced to differentiate by exposure to LPS, they secrete IgM that is hemolytic for both SRBC and BrMRBC and that carries a recognizable idiotype. We looked in the spleens of normal mice for cells with these same characteristics (Bishop & Haughton 1985).…”

Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline.

“…(9) in hybridomas generated from normal spleen cells and selected for the ability to lyse BrMRBC. The idiotype associated with a second combination had been detected on Ly-1 B cells in the spleen of normal mice (14). Since PtC-specific antibodies produced by peritoneal B cells of Bl0.H-2°H-46p/Wts (2a4b) mice are firmly established as belonging to the Ly-1 B cell population (4), we generated a panel of hybridomas from PerC of these mice.…”