Cellular composition of germinal centers in lymph nodes after HIV-1 infection: Evidence for an inadequate support of germinal center B lymphocytes by follicular dendritic cells

Abstract

Germinal centers in lymph nodes with follicular hyperplasia from 15 patients with HIV-1 infection were analyzed by qualitative and quantitative electron microscopical methods and compared with control follicular hyperplasia (FH). Using a pattern recognition method, two main clusters were recognized within the germinal centers of HIV and FH lymph nodes on the basis of the relative frequencies of small centroblast and centrocytes. All FH lymph nodes and 6 HIV-1 lymph nodes (HIV-Clu-1) were placed in cluster 1; 9 HIV-1 lymph nodes (HIV-Clu-2) formed cluster 2. Germinal centers in the HIV-Clu-2 lymph nodes were characterized by a cell composition of predominantly lymphoid blasts and decreased numbers of centrocytes, but without altered numbers of mitotic figures. The frequency distribution of ultrastructurally distinct FDC subtypes differed between these clusters. In HIV-Clu-2 the frequencies of FDC types with an undifferentiated and regressive morphology occurred at a higher frequency, whereas FDC types with a highly differentiated morphology had a lower frequency. We conclude that 9 out of 15 lymph nodes with HIV-1 associated follicular hyperplasia show changes in FDC morphology indicative of a less differentiated functional stage of FDC. The changes in FDC morphology are closely associated with changes in the germinal center B-cell population resulting in an inverted blast to the centrocyte ratio.