B cell stimulatory effects of alpha-enolase that is differentially expressed in NZB mouse B cells.
Intrinsic polyclonal B cell activation is characteristic of NZB mice and it contributes to the development of lupus nephritis in NZB crosses. Although multiple autosomal genes appear to be involved, the major loci for B cell hyperactivity have been mapped on chromosome 4. To identify various genes determining B cell hyperactivity, differential mRNA display was done comparing B cells of NZB and BALB/c mice. The approach yielded 32 genes that were consistently upregulated in NZB B cells. Among these, alpha-enolase, which is located in the region of chromosome 4 containing B cell hyperactivity loci, was found to be spontaneously overexpressed only in NZB B cells, but not in splenic B or T cells of BALB/c or T cells of NZB mice. Exposure to soluble, but not plate-bound, enolase induced splenic B cells from normal BALB/c mice or B cell lymphoma lines to secrete Ig that was mediated by augmented transcription. Moreover, in combination with a subthreshold stimulus with anti-IgM, enolase augmented the expression of CD69 and B7.2 in nai;ve B cells from normal mice. Enolase probably functions intracellularly as an accessory molecule in stimulating B cells. Since functionally related genes tend to congregate, enolase may contribute to polyclonal B cell activation in cooperation with other genes in the hyperactivity loci, which appear to be in a transcriptionally active region in NZB B cells.
Babu
John Sam
JS
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Sun
Tiedan
T
Xu
Luting
L
Datta
Syamal K
SK
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D005786:Gene Expression Regulation; D007075:Immunoglobulin M / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation
D007075:Immunoglobulin M; D012333:RNA, Messenger; D010751:Phosphopyruvate Hydratase