rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues.
Human C5a is a potent chemoattractant for granulocytes, monocytes, and dendritic cells. In mice C5a has been shown to be chemotactic for germinal center (GC) B cells. To date, no information is available on the effects of C5a on human B cell locomotion. Here we demonstrate that rC5a increases polarization and migration of human tonsillar B cells. The locomotory response was due to both chemokinetic and chemotactic activities of rC5a. Moreover, memory and, at a lesser extent, naive B cell fractions from purified tonsillar populations displayed rC5a-enhanced migratory properties, whereas GC cells did not. Flow cytometry revealed C5aR (CD88) on approximately 40% memory and 10% naive cells, respectively, whereas GC cells were negative. Immunohistochemistry showed that a few CD88+ cells were of the B cell lineage and localized in tonsillar subepithelial areas, where the majority of memory B cells settle. Pretreatment of memory B cells with the CD88 mAb abolished their migratory responsiveness to rC5a. Finally, the C5 gene was found to be expressed in naive, GC, and memory B lymphocytes at both the mRNA and the protein level. This study delineates a novel role for C5a as a regulator of the trafficking of human memory and naive B lymphocytes and supports the hypothesis that the B cells themselves may serve as source of C5 in secondary lymphoid tissues.
Ottonello
L
L
Department of Internal Medicine, University of Genova, Italy. otto@csita.unige.it
Corcione
A
A
Tortolina
G
G
Airoldi
I
I
Albesiano
E
E
Favre
A
A
D'Agostino
R
R
Malavasi
F
F
Pistoia
V
V
Dallegri
F
F
D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology; D003182:Complement C5 / Q000096:biosynthesis / Q000235:genetics; D015936:Complement C5a / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000096:biosynthesis / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology*
D015703:Antigens, CD; D002630:Chemotactic Factors; D003182:Complement C5; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011994:Recombinant Proteins; D015936:Complement C5a