SummaryMechanisms of tumor development were studied in SCID mice injected with human lymphoid cells from Epstein-Barr virus-positive (EBV +) donors. About 80% of peripheral blood mononuclear cell (PBMC)-injected animals developed a lymphoproliferative disease associated with oligoclonal EBV + tumors of human B cell origin. No change in tumor development rate occurred when monocyte-depleted PBMC were inoculated. No tumors developed when purified B cells were injected. B cell lymphoproliferative disease was also prevented in most cases when PBMC-injected animals were treated with agents that prevent T cell activation, such as cyclosporin A. Both CD4 § and CD8 + T cell subpopulations were able to provide putative factor(s) necessary for EBV + B cell expansion and progression to tumors. These data suggest that the transfer alone of potentially tumorigenic human cells into an immunodeficient environment, such as the SCID mouse, might not be sufficient for cell progression to tumor, and raise the possibility that chronic activation events could play a major role in the pathogenesis of some EBV + lymphomas in the immunocompromised host.

Following the observation of Bonnefoy et al. (J. Exp. Med. 1988. 167:57), that the low-affinity IgE receptor (CD23) on B lymphocytes can be coupled (with the use of chemical cross-linking reagents) to major histocompatibility complex (MHC) class II DR molecules, we now report that ligands binding within the lectin-homology region of CD23 prevent B cells from stimulating allogeneic mixed lymphocyte responses. Ligands capable of blocking mixed lymphocyte responses include the anti-CD23 antibodies MHM6 and EBVCS 4 but not EBVCS 1 and 5. IgE itself, and small peptides representing sequences within the CH3 domain of IgE. The detailed topographical relationship between CD23 and MHC class II on the B lymphocyte surface was examined using dual immuno-fluorescence labeling of cells and direct visualization of the staining by confocal laser scanning microscopy. On transformed B lymphoblasts, the two antigens were seen to co-localize in discrete patches; on normal B cells which had been cultured for 2 days with interleukin 4, CD23 and MHC class II converged at a single pole which exhibited a tendency to pseudopod formation and provided a focus for homotypic cell-cell interactions. The possibility that CD23 could serve as a co-stimulatory-adhesion molecule in antigen presentation by B lymphocytes is discussed with special reference to a potential role in the regulation of IgE synthesis.

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B cell dysregulation is a hallmark of human immunodeficiency virus infection. Since B lymphocytes comprise two distinct subpopulations, CD5+ and CD5- cells, we addressed their individual phenotypic and functional behavior. Seropositive patients with both limited and advanced disease progression had an increased percentage of peripheral blood CD5+ B cells, compared to seronegative controls (20.1 +/- 2.1 and 22.7 +/- 5.7, respectively, vs 17.0 +/- 3.4 in controls); however, due to the lymphopenia and reduced number of circulating B cells in infected individuals, the absolute number of CD19+CD5+ lymphocytes was actually reduced. Although HIV-specific antibodies were synthesized spontaneously in vitro only by CD5- B cells, a 10-fold lower degree of spontaneous, non-HIV-specific activation was also displayed by unstimulated CD5+ B cells. These findings indicate that B cell dysregulation during HIV infection involves both the CD5- and the CD5+ B cell compartments; moreover, in view of the putative role of CD5+ B cells in autoimmune phenomena and IL-10 production, these data reinforce the possibility that B cell dysfunction might be causally involved in AIDS pathogenesis.