By means of mixed agglutination test and indirect immunofluorescence test, reactions of infectious mononucleosis sera with bone marrow cells were investigated. Positive reactions were observed with bovine, murine and rat bone marrow cells, but negative results were obtained with cells of monkeys and guinea pigs. Absorption studies demonstrated that the observed reactions are due to interaction of the Paul-Bunnell antigen on bone marrow cells with its corresponding antibodies in infectious mononucleosis sera. Whereas all cells of bovine bone marrow gave positive results, only 50% of murine or rat cells were positive and these cells were shown to be neutrophilic granulocytes. Evidence was also presented that the Paul-Bunnell antigen and Fc receptor are present, apart from each other, on murine neutrophilic granulocytes.
The developmental process of human antibody (Ab)-secreting B cells in humanized mice is not fully defined. To examine the characteristics of class-switched and Absecreting B cells in humanized mice, we analyzed NOD/Shi-scid, common γc-null mice reconstituted with cord blood-derived hematopoietic stem cells (CB-NOG). Most of the CD138-positive plasmablasts (PBs)/plasma cells (PCs) in the NOG spleen maintained CD5 expression. Moreover, IgG-bearing B cells, including PBs and memory cells, predominantly had a CD21-CD24hiCD5+ phenotype. We examined the expression of CD21, CD24 and CD5 on B cells developed in CB-NOG mice. We observed three types of B cells (CD24high CD21-; T1, CD24low/CD21-; T2, CD24-CD21 + ; T3) within CB-NOG CD5+ cells, which are similar to transitional B cells. However, the surface marker expression was different from normal transitional B cells. First, CD21 expression was significantly lower than in human peripheral blood and CB-derived mature B cells. Second, the expression of CD5 increased according to the developmental stage. The splenocytes were sorted according to the transitional subsets and examined for IL-10 expression. The CD21-CD24hiCD5+ fraction had the highest IL-10 expression among the CD5 + cells, suggesting the involvement of regulatory B cells. The same fractions were cultured in the presence of CpG and IgM. These stimulated B cells secreted a low level of IgM and IgG Abs to CpG and IgM stimulation in vitro and maintained a CD5+CD21low phenotype. These results demonstrate that IgG-bearing B cells with a CD21-CD24hiCD5+ irregular phenotype are developed in humanized NOG mice and have become the source of antibodies in CB-NOG mice. (250 words).
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