Chemotaxis of germinal center B cells in response to C5a.
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.
Department of Microbiology and Immunology, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298-0678.
L I
LI
Kupp
M H
MH
Kosco
H A
HA
Schenkein
J G
JG
Tew
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000276:immunology*; D005260:Female; D007249:Inflammation / Q000503:physiopathology*; D008070:Lipopolysaccharides; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D013997:Time Factors; D015054:Zymosan / Q000494:pharmacology
D008070:Lipopolysaccharides; D015936:Complement C5a; D015054:Zymosan