Antigen-Engaged B Cells Undergo Chemotaxis toward the T Zone and Form Motile Conjugates with Helper T Cells

Abstract

Interactions between B and T cells are essential for most antibody responses, but the dynamics of these interactions are poorly understood. By two-photon microscopy of intact lymph nodes, we show that upon exposure to antigen, B cells migrate with directional preference toward the B-zone–T-zone boundary in a CCR7-dependent manner, through a region that exhibits a CCR7-ligand gradient. Initially the B cells show reduced motility, but after 1 d, motility is increased to approximately 9 μm/min. Antigen-engaged B cells pair with antigen-specific helper T cells for 10 to more than 60 min, whereas non-antigen-specific interactions last less than 10 min. B cell–T cell conjugates are highly dynamic and migrate extensively, being led by B cells. B cells occasionally contact more than one T cell, whereas T cells are strictly monogamous in their interactions. These findings provide evidence of lymphocyte chemotaxis in vivo, and they begin to define the spatiotemporal cellular dynamics associated with T cell–dependent antibody responses.

CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

“…delivery of very low amounts of DNA), antigen-specific B cells may enrich antigen via their (antigenspecific) surface receptors and subsequently present antigen to T cells (predominantly CD4 þ T cells) in lymphatic tissues. 46,47,51,52 Assuming that in fact antigen-presenting B cells play an important role for the adjuvant activity of CCL19 in the mouse model used in our study, it still remains an open question as to why CCL19 leads to an amplification of CD8 þ T-cell responses in mMT mice, but not in WT mice. Nevertheless, it has been previously concluded from experimental mouse models 53,54 that B cells are crucial for the development of TH2 responses by triggering IL-4 production in T cells or that they may even suppress tumor immunity, 55 possibly by competition with other APC as has previously been suggested by Qin et al 56 Since Her2/neu-directed immune responses after gene gun immunization are mediated by T cells, antibodies and many other immune mechanisms, 44 Her2/neu-specific T cells in B-cell-deficient mice (which contain higher numbers of T cells than WT mice, data not shown) might partially compensate for the lack of anti-Her2/neu antibodies, thereby re-establishing a direct correlation between tumor protection and ex vivo T-cell responses.…”

3D and 4D imaging of immune cells in vitro and in vivo

“…Therefore, many imaging studies were done in this lymph node (Lindquist et al 2004;Miller et al 2003;Okada et al 2005). For its preparation, the experimental animal is transferred to a heated platform or water bath.…”

The Biophysics of T Lymphocyte Activation In Vitro and In Vivo

“…During the co-migration, very motile T cells were shown to push B cells in vivo through lymph node parenchyma, whereas B cells, when activated, may take the lead themselves and pull T cells [34]. The latter finding was later confirmed for B cells which were activated by loading antigen onto their B cell receptor [32]. Another issue covered by the studies mentioned was directional migration.…”

“…However, B cells may also actively participate in antigen presentation, if they were able to internalize soluble antigen via their B cell receptor, process the antigen and load the generated peptides onto MHC molecules an then transport these MHC/peptide complexes to the cell surface [31]. B cells will then migrate with directional preference toward the B-zone-T-zone boundary by upregulating the chemokine receptor CCR7, which enables the B cells to sense a CCR7-ligand gradient, which extends from the T zone into the border of the B cell follicle [32,33]. Immigrant T cells will start scanning the surrounding APCs for a peptide/MHC complex capable of binding with high affinity to their TCR.…”

“…Another important function of helper cells is to support the generation of cytotoxic effector cells. Consequently, a part of the pre-activated CD4 + T cell will march towards the lymph node's B cell zone [32], while others stay in the T cell zone or leave the lymph node to function in the periphery [38]. A CD8 + cell, in contrast, would turn into a cytotoxic T cell (CTL) possessing various direct and indirect possibilities of killing infected cells.…”