Tinigible Body Macrophages in Regulation of Germinal Center Reactions

Abstract

Tingible body macrophages (TBM), long thought simply as scavengers of apoptotic lymphocytes, are located in the unique microenvironment of germinal centers in close proximity to antigen-retaining follicular dendritic cells (FDC). Observations that TBM endocytose FDC-iccosomal (immune-complex coated bodies) antigen suggested that TBM might present this antigen and help regulate the germinal center reaction. To test for antigen presentation, the ovalbumin (OVA)-specific TH hybridoma, 3DO-54.8, which produces IL-2 on receiving effective presentation of OVA, were used as responders to OVA-bearing TBM. Results showed that OVA-bearing TBM failed to induce IL-2 production. Furthermore, addition of TBM to IL- 2-inducing positive controls (B cells) not only failed to augment IL-2 production, but rather TBM significantly (55-90%) reduced B-cell induction of IL-2. We found that TBM were rich in prostaglandin by comparison with other nongerminal center lymph node macrophages and that addition of indomethacin to the cultures reversed the inhibitory effect of TBM. Depletion of TBM from enriched preparations, prior to addition to positive control cultures, also abrogated the inhibitory effect on IL-2 production. These data support the concept that TBM, within the unique microenvironment of germinal centers, may be specialized to downregulate the germinal center reaction.

CD4 + T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

“…Notably, iBALT in nonreactivators exclusively harbored tingible body macrophages (Fig. 8G), specialized macrophages that are involved in germinal-center reactions (35) and that are especially critical for the phagocytosis of apoptotic B cells undergoing affinity maturation (36). Overall, our findings indicate that protection from reactivation of Mtb infection occurs independently of CD4 + T-cell depletion and correlates rather with increased levels of iBALT.…”

“…Although the precise role of B cells in TB infection control remains to be determined, existing evidence suggests that B cells are required for optimal development of immune responses against Mtb (15,16,41). Moreover, the presence of tingible body macrophages in BALT suggests that B cells are undergoing affinity maturation or that cross-priming of CD8 + T cells occurs within these lymphoid follicles, allowing site-directed activation of macrophages (33,35,42,43). We postulate that these protective lymphoid follicles proximal to the granuloma lead to localized T-cell activation and enhanced B-cell and humoral immunity.…”

Receptor-type protein tyrosine phosphatase gamma (PTPγ), a new identifier for myeloid dendritic cells and specialized macrophages

“…Their main role in germinal center reaction is related to the scavenger function of apoptotic germinal center B cells (for reviews, see MacLennan 42 and Smith et al 43 ). We found that they expressed PTP␥ and physically interacted with germinal center T cells.…”

Temporary Blockade of the Tumor Necrosis Factor Receptor Signaling Pathway Impedes the Spread of Scrapie to the Brain

“…Therefore, the detection of severe and extensive lymphocyte apoptosis following treatment with huTNFR:Fc suggested that this was most likely due to a loss of mature FDCs. Many of these apoptotic B lymphocytes were identified whole within tingible body macrophages which scavenge apoptotic lymphocytes and are considered to regulate the germinal-center reaction (42). The increased survival time following treatment with huTNFR:Fc is unlikely to be directly related to a loss of B lymphocytes by apoptosis, as ME7 scrapie pathogenesis is unaffected in mice with impaired germinal-center B-lymphocyte development (30).…”