Abstract 544: Follicular Dendritic Cells promote tumor B cell survival through BAFF mediated anti-apoptotic signaling in the tumor microenvironment of Follicular Lymphoma

Serum antibody (Ab) can play several roles during B cell immune responses. Among these is to promote the deposition of immune complexes (ICs) on follicular dendritic cells (FDCs). ICs on FDCs are generally thought to be critical for normal germinal center (GC) formation and the development and selection of memory B cells. However, it has been very difficult to test these ideas. To determine directly whether FDC-bound complexes do indeed function in these roles, we have developed a transgenic (Tg) mouse in which all B lymphocytes produce only the membrane-bound form of immunoglobulin M. Immune Tg mice have 10,000-fold less specific Ab than wild-type mice and lack detectable ICs on FDCs. Nonetheless, primary immune responses and the GC reaction in these mice are robust, suggesting that ICs on FDCs do not play critical roles in immune response initiation and GC formation. Moreover, as indicated by the presence and pattern of somatic mutations, memory cell formation and selection appear normal in these IC-deficient GCs.

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Disruption of Follicular Dendritic Cells–Follicular Lymphoma Cross-talk by the Pan-PI3K Inhibitor BKM120 (Buparlisib)

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-14-0154 ◽

2014 ◽

Vol 20 (13) ◽

pp. 3458-3471 ◽

Cited By ~ 14

Author(s):

Alba Matas-Céspedes ◽

Vanina Rodriguez ◽

Susana G. Kalko ◽

Anna Vidal-Crespo ◽

Laia Rosich ◽

...

Keyword(s):

Dendritic Cells ◽

Follicular Lymphoma ◽

Cross Talk ◽

Pi3k Inhibitor ◽

Follicular Dendritic Cells ◽

Follicular Dendritic

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B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells

Blood ◽

10.1182/blood-2009-06-229567 ◽

2009 ◽

Vol 114 (24) ◽

pp. 4989-4997 ◽

Cited By ~ 68

Author(s):

Marc Bajénoff ◽

Ronald N. Germain

Keyword(s):

Dendritic Cells ◽

T Cell ◽

B Cell ◽

Soluble Antigen ◽

Antigen Delivery ◽

Follicular Dendritic Cells ◽

Conduit System ◽

Follicular Dendritic ◽

Conduit Network ◽

Cell Zone

Abstract Afferent lymph is transported throughout lymph nodes (LNs) by the conduit system. Whereas this conduit network is dense in the T-cell zone, it is sparse in B-cell follicles. In this study, we show that this differential organization emerges during lymph node development. Neonatal LNs lack B follicles, but have a developed T-cell zone and a dense conduit network. As new T and B cells enter the developing LN, the conduit network density is maintained in the T, but not the B zone, leading to a profound remodeling of the follicular network that nevertheless maintains its connectivity. In adults, the residual follicular conduits transport soluble antigen to deep regions, where follicular dendritic cells are abundant and appear to replace the fibroblastic reticular cells that enwrap conduits in the T zone. This strategic location correlates with the capacity of the follicular dendritic cells to capture antigen even in the absence of antigen-specific antibodies. Together, these results describe how the stromal organization of the T and B regions of LNs diverges during development, giving rise to distinct antigen transport and delivery modes in the 2 compartments.

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