Differential regulation of germinal center genes, BCL6 and SWAP-70, duringthe course of MAIDS

Germinal centers (GC) are the sites of antigen-driven B cell switch recombi nation, V(D)J gene hypermutation, and selection to generate hi,oh-affinity CD38(+) memory B cells. A marked expansion of GC associated with hypergamma globulinemia followed by complete disruption of normal splenic architecture and a striking drop in immunoglobulin levels are prominent features of the murine retrovirus-induced immunodeficiency syndrome, MAIDS. B cell lymphom as are frequent in long-term infected mice. Normal GC formation is critical ly dependent on a number of genes including the transcription factor, Bcl6. Deregulated expression of BCL6 protein has been implicated in the developm ent of human and mouse B cell lymphomas. Another nuclear protein, SWAP-70, has been identified as a subunit of the protein complex, SWAP, that recombi nes switch regions in vitro. To develop a fuller understanding of B cell bi ology in MAIDS, we examined the characteristics of BCL6, SWAP-70, CD38, and peanut agglutinin (PNA)-staining cells during the course of the disease. T he levels of both nuclear proteins increased rapidly until 6-8 weeks after infection. During this time frame, BCL6 was expressed at highest levels in the usually rare CD4(+) Thy1(-) T cell subset as well as in B cells. Ar lat er times, BCL6 levels dropped to undetectable levels while SWAP-70 levels c ontinued to increase. Changes in the levels of either protein could not be ascribed to transcriptional regulation. PNA-reactive cells decreased in con cert with BCL6 while CD38 staining increased with SWAP-70. These results de monstrate that progression of MAIDS results in the massive accumulation of B cells with the morphology of secretory cells that behave like post-GC cel ls for expression of BCL6 and CD38. and for PNA-staining but with abnormall y high-level expression of SWAP-70. Published by Elsevier Science Ltd.