Patients with drug-free long-term graft function display increased numbers of peripheral B cells with a memory and inhibitory phenotype.
Several transplant patients maintain stable kidney graft function in the absence of immunosuppression. Here we compared the characteristics of their peripheral B cells to that of others who had stable graft function but were under pharmacologic immunosuppression, to patients with chronic rejection and to healthy volunteers. In drug-free long-term graft function (DF) there was a significant increase in both absolute cell number and frequency of total B cells; particularly activated, memory and early memory B cells. These increased B-cell numbers were associated with a significantly enriched transcriptional B-cell profile. Costimulatory/migratory molecules (B7-2/CD80, CD40, and CD62L) were upregulated in B cells; particularly in memory CD19(+)IgD(-)CD38(+/-)CD27(+) B cells in these patients. Their purified B cells, however, responded normally to a polyclonal stimulation and did not have cytokine polarization. This phenotype was associated with the following specific characteristics which include an inhibitory signal (decreased FcgammaRIIA/FcgammaRIIB ratio); a preventive signal of hyperactive B-cell response (an increase in BANK1, which negatively modulates CD40-mediated AKT activation); an increased number of B cells expressing CD1d and CD5; an increased BAFF-R/BAFF ratio that could explain why these patients have more peripheral B cells; and a specific autoantibody profile. Thus, our findings show that patients with DF have a particular blood B-cell phenotype that may contribute to the maintenance of long-term graft function.
INSERM U643, and Institut de Transplantation et de Recherche en Transplantation, 30 Boulevard Jean Monnet, Nantes Cedex 01, France.
Annaick
A
Pallier
Sophie
S
Hillion
Richard
R
Danger
Magali
M
Giral
Maud
M
Racapé
Nicolas
N
Degauque
Emilie
E
Dugast
Joanna
J
Ashton-Chess
Ségolène
S
Pettré
Juan José
JJ
Lozano
Régis
R
Bataille
Anne
A
Devys
Anne
A
Cesbron-Gautier
Cécile
C
Braudeau
Catherine
C
Larrose
Jean-Paul
JP
Soulillou
Sophie
S
Brouard
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000032:analysis; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007108:Immune Tolerance; D007156:Immunologic Memory; D007518:Isoantibodies / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000502:physiology; D008875:Middle Aged; D010641:Phenotype
D048868:Adaptor Proteins, Signal Transducing; D018941:Antigens, CD19; D001323:Autoantibodies; C447641:BANK1 protein, human; D007518:Isoantibodies; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1