Chemotaxis of germinal centers B cells in response to C5a

Abstract

An infiltrate of B cells and plasma cells is characteristic of certain chronic inflammatory lesions. However, mechanisms involved in the local accumulation of these cells have not been established. Efforts to demonstrate that B cells from normal animals can migrate in response to inflammation-induced chemoattractants have been inconclusive. The objective of this study was to determine if murine germinal center (GC) B cells could respond chemotactically to a C5a gradient. On successive days after secondary immunization, draining lymph nodes were harvested and the activated GC B cells isolated. These GC B cells were placed in modified Boyden chambers, incubated for 3 h and the distance the leading front of cells migrated through the filters was determined. The results show that GC B cells migrated to factors in zymosan- and lipopolysaccharide-activated serum. The migratory response demonstrated distinct kinetics. Cells isolated between 2 to 4 days after secondary immunization migrated, whereas cells isolated at day 0 and beyond day 6 did not. Checkerboard analysis revealed that the migratory response was attributable to both chemokinesis and chemotaxis. Anti-C5 inhibited the migration of day-3 GC B cells implicating C5 in the migration mechanism. Studies using recombinant C5a established that this C5 fragment was chemotactically active. In conclusion, GC B cells generally were not chemotactically active. However, at a particular stage of maturation B cells in the GC become responsive to C5a as a chemotactic agent. Thus, B cells from normal animals may respond chemotactically, and C5a may play a role in recruitment of recently activated B cells into inflammatory sites.

The Dendritic Cell-Specific CC-Chemokine DC-CK1 Is Expressed by Germinal Center Dendritic Cells and Attracts CD38-Negative Mantle Zone B Lymphocytes

“…Ultimately, both T and B cells have to localize inside B cell follicles to initiate a GC reaction. Recruitment of preactivated B and T lymphocytes into the follicle can be guided by BCA-1, DC-CK1, the classic chemoattractant C5a (28,31), fractalkine (CX3CL1), and maybe by other yet unknown chemokines expressed in follicles. In this way, both activated Ag-specific T and B cells are able to migrate toward follicles, where they interact with GCDC and FDC resulting in the development of GC reactions and memory B cell formation (21,23).…”

Complement and its role in innate and adaptive immune responses

“…B cells have been reported to express C3aR; and both ligands, C3a and C3a desArg , have been shown to negatively regulate the polyclonal immune response, as well as limit the secretion of TNF-α and IL-6 [103,104]. Conversely, C5a has been reported to play a role in the trafficking and migration of various B-cell populations, including GC B cells and tonsillar memory and naїve B cells [105][106][107].…”

Complement Receptors in Inflammation

“…C5aR is a powerful chemoattractant receptor for monocytes (Pieters et al, 1995), neutrophils (Webster et al, 1980), eosinophils (DiScipio et al, 1999), basophils (Lett-Brown and Leonard, 1977), mast cells (Hartmann et al, 1997), B cells (Kupp et al, 1991) and T cells (Nataf et al, 1999). It also stimulates mast cell degranulation , mast cell chemotaxis in specific mast cell subtypes (Hartmann et al, 1997, McCloskey et al, 1999, oxidative burst in granulocytes and the production of reactive oxygen species (ROS) in neutrophils , secretion of lysosomal enzymes from macrophages (McCarthy and Henson, 1979) and polymorphonuclear (PMN) cells as well as the secretion of proinflammatory mediators from monocytes, eosinophils (Takafuji et al, 1994) and mast cells (Hartmann et al, 1997).…”