Follicular dendritic cells and B cell chemotaxis

Abstract

B cells isolated from germinal centers (GC) of immune mice 2-5 days after antigen (Ag) challenge migrate in response to chemotactic signals, whereas GC B cells isolated at other times and resting B cells do not. Since B cells are in direct contact with follicular dendritic cells (FDC) in GC we reasoned that FDC might play a role in enabling B cells to become chemotactically active. Resting B cells were co-cultured with FDC either with or without anti-mu-dextran (anti-mu-dex) as an Ag surrogate and/or recombinant interleukin (rIL)-4 as a T cell surrogate. After 3 days, the B cells were isolated and their migration to chemotactic factors contained in zymosan-activated serum assessed in microchemotaxis chambers. B cells incubated alone or with anti-mu-dex or rIL-4 showed minimal migration, which could be increased if both anti-mu-dex or rIL-4 were present. However, maximal migration was obtained when B cells were cultured with FDC, and this was not increased by addition of anti-mu-dex and/or rIL-4, indicating that the FDC signal was a primary signal and did not require pre-activation of the B cells. Checkerboard analysis using variation in concentration and location of the chemoattractant in chemotaxis chambers indicated that both chemotaxis and chemokinesis occurred. B cell migration began within 6 h of culture, peaked by 48 h and decreased thereafter. Removal of FDC or interference with FDC-B cell contact ablated or significantly decreased induction of B cell migration. Furthermore, induction did not require functional T cells. These data indicate that FDC can induce resting B cells to become responsive to chemotactic signals.

Persistence of Infectious HIV on Follicular Dendritic Cells

“…The next day, HIV-1 IIIB (50 l of a stock cell-free virus suspension containing 28 ng of p24) was injected in each of the hind and fore feet to allow immune complex formation and FDC trapping in multiple draining lymph nodes. Mice were rested for the indicated times, their draining lymph nodes excised, and the FDCs isolated according to previously published procedures (15,16). Our FDC-enriched preparations routinely contained 25-50% FDCs with contaminants of equal numbers of T and B lymphocytes.…”

“…We isolated cells from mice injected 1 mo earlier with HIV and depleted the FDC population from one portion by means of a biotin-conjugated anti-mouse FDC Ab and streptavidin-magnetic beads. This procedure generates both FDCdepleted (Ͻ10% FDCs) and purified (Ͼ90% FDCs) fractions (16). Ten thousand FDC-depleted cells, FDC-enriched (i.e., not fractionated), or purified FDCs were then cocultured with H9 target cells.…”

Regulation of Follicular Dendritic Cell Networks by Activated T Cells: The Role of CD137 Signaling

“…The formation and maintenance of GC depend on the dynamic interactions among B cells, T cells, and FDCs (1)(2)(3). FDCs play important roles in GC B cell proliferation, survival, and differentiation in both Ag-dependent and -independent manners (4,5), whereas activated T cells induce the differentiation of GC B cells by providing CD40L and cytokines (6). When Abs are produced during a primary immune response, Ab-Ag complexes are formed and trapped for long periods of time on FDCs due to abundant Ig Fc and complement receptors (CR), among which CR1 and CR2 are the key immune complex-trapping molecules within primary follicles (2,7).…”

“…When Abs are produced during a primary immune response, Ab-Ag complexes are formed and trapped for long periods of time on FDCs due to abundant Ig Fc and complement receptors (CR), among which CR1 and CR2 are the key immune complex-trapping molecules within primary follicles (2,7). FDCs then present intact Ag for recognition by B cells, which is believed to be crucial for the development of high affinity, isotype-switched, and memory B cell responses (4,5,8,9). In addition to delivering Ag, FDCs seem to supply numerous nonspecific stimuli during GC responses for the generation of an optimal B cell response (10).…”

Quantification of cellular adhesion molecules on malignant B cells from non-Hodgkin’s lymphoma

“…Stromal cells are also essential in the environment of B lymphocytes and CD54, LFA-1, as well as CD29/CD49d, have also been implicated in adhesion to fibroblasts 45 or follicular dendritic cells. 2,16,18 The strong correlation (P Ͻ 0.0001) between CD54 expression on malignant cells and Ki67, a marker of cell proliferation and tumour aggressiveness, also supports the idea that tumour behaviour could involve privileged contacts with neighbouring cells. Preferential interaction with the microenvironment has also been described in myeloma, in which LFA-1 expression has been correlated with active disease and with high labelling index.…”