Submitted August 21, 2007
Accepted October 3, 2007
Increased survival is a selective feature of human circulating antigen-induced plasma cells synthesizing high affinity antibodies
Ines Gonzalez-Garcia, Beatriz Rodriguez-Bayona, Francisco Mora-Lopez, Antonio Campos-Caro, and Jose A Brieva*
Servicio de Inmunologia and Unidad de Investigacion, Hospital Universitario Puerta del Mar, Cadiz, Spain
* Corresponding author; email: josea.brieva.sspa{at}juntadeandalucia.es.
The present study shows that tetanus toxoid (tet)-booster releases to the human circulation two subsets of specific plasma cells (PC), as defined by phenotype and morphology, which clearly differed in the staining capacity of their cytoplasmic antibodies (Ab) with FITC-labeled tet-fragment C (tetC). These cells, termed tetCHIGH and tetCINT PC according to their either high or intermediate tetC-FITC staining-capacity, exhibit similar rapid temporal kinetics in the blood (5th-8th days post-boost), contain many cycling cells, express equivalent amounts of BLIMP-1 mRNA and produce similar quantities of IgG. However, Ab synthesized by tetCHIGH PC show a tetC-affinity more than 10 times higher than that exhibited by tetCINT PC Ab, and indicated by IGVH sequence analysis. Chemotaxis to CXCL12, a requisite for BM PC homing, is similar for both cell types. Circulating non-specific and tetCINT PC, but not tetCHIGH PC, 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 two discrete subsets of specific PC exhibiting different ranges of Ab-affinity for the immunogen, and that only those synthesizing high-affinity Ab show enhanced survival. This inherent property may be essential for determining the BM fate of PC secreting high-affinity Ab.
