Increased survival is a selective feature of human circulating antigen-induced plasma cells synthesizing high-affinity antibodies.
The present study shows that tetanus toxoid (tet) booster releases to the human circulation 2 subsets of specific plasma cells (PCs), as defined by phenotype and morphology, which clearly differed in the staining capacity of their cytoplasmic antibodies (Abs) with fluorescein isothiocyanate (FITC)-labeled tet-fragment C (tetC). These cells, called tetCHIGH and tetCINT PCs according to their either high or intermediate FITC-tetC staining capacity, exhibit similar rapid temporary kinetics in the blood (5-8 days after boost), contain many cycling cells, express equivalent amounts of BLIMP-1 mRNA, and produce similar quantities of IgG. However, Abs synthesized by tetCHIGH PCs show a tetC affinity more than 10 times higher than that exhibited by tetCINT PC Abs, and indicated by IGVH sequence analysis. Chemotaxis to CXCL12, a requisite for bone marrow (BM) PC homing, is similar for both cell types. Circulating nonspecific and tetCINT PCs, but not tetCHIGH PCs, tend to undergo spontaneous apoptosis, as demonstrated by APO2.7 and activated caspase-3 expression, and cell recovery. These results indicate that tet booster generates 2 discrete subsets of specific PCs exhibiting different ranges of Ab affinity for the immunogen, and that only those synthesizing high-affinity Abs show enhanced survival. This inherent property may be essential for determining the BM fate of PCs secreting high-affinity Ab.
González-García
Inés
I
Servicio de Immunología and Unidad de Investigación, Hospital Universitario Puerta del Mar, Cádiz, Spain.
Rodríguez-Bayona
Beatriz
B
Mora-López
Francisco
F
Campos-Caro
Antonio
A
Brieva
José A
JA
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology*; D000915:Antibody Affinity / Q000187:drug effects / Q000276:immunology*; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D053148:Caspase 3 / Q000276:immunology; D054377:Chemokine CXCL12 / Q000276:immunology / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012097:Repressor Proteins / Q000276:immunology; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors; D014157:Transcription Factors / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D012097:Repressor Proteins; D013745:Tetanus Toxoid; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053148:Caspase 3