Gaucher disease is associated with lymph node reactive follicular hyperplasia with tingible body macrophages of M2 phenotype

In Gaucher disease (GD), deficiency of the lysosomal enzyme, acid β-glucocerebrosidase (GCase), and subsequent accumulation of its substrate in macrophages leads to inappropriate immune activation. GCase deficiency affects the differentiation of the mononuclear phagocyte lineage with the resultant dysfunction of reticuloendothelial system organs including liver, spleen and lymph nodes. While lymphadenopathy is often observed in GD, the underlying mechanisms are unknown. We studied the pathophysiology of lymph node enlargement in a case with Gaucher disease (N370S/RecNciI) and monoclonal gammopathy of undetermined significance (MGUS). Reactive follicular hyperplasia with intrafollicular monotypic plasma cells (IgG kappa) was observed in lymph node biopsy with presence of variably sized follicles in polarized germinal centers and macrophage infiltration. Dual fluorescence labeling with macrophage (M2) marker and Ki67, a marker of proliferative activity, indicated that the lesion was composed of active and proangiogenic macrophages. The immunophenotyping of peripheral blood showed clonal B-cell proliferation, and a reduced number of circulating marginal zone memory B-cells. M2 macrophages promote tumor formation through cell-to-cell interaction by differentiating into tumor-associated macrophages. M2 cells also promote vascularization and formation of lymphatic vessels. This data not only highlights the mechanisms of lymphadenopathy in GD, but also may bridge the gap between the cell types interplaying in the development of B cell related disorders.