Alterations in the peripheral blood B cell subpopulations of multidrug-resistant tuberculosis patients.
The function of B cells in the immune response against Mycobacterium tuberculosis (Mtb) is still regarded as secondary, although major findings in mouse models of tuberculosis (TB) support their participation as regulators and antibody producers. However, studies in cohorts of TB or multidrug-resistant TB (MDR-TB) patients have failed to clearly identify changes in the circulating B cell pool. Therefore, in the present study we aimed at identifying alterations in the different B cell subpopulations in peripheral blood samples of HIV-negative pulmonary MDR-TB patients when compared to healthy donors. The data show, for the first time, that MDR-TB patients, similarly to what has been observed in other chronic inflammatory diseases, have a much lower frequency of peripheral blood unswitched IgD(+)CD27(+) memory B cells. Equally novel are the findings that in MDR-TB patients there is a reduction in the circulating plasma cell pool and that in MDR-TB there is an increased frequency of circulating type 1 transitional IgD(+)CD38(++), CD69(+) and TLR9(+) B cells. These results document disease-related shifts in peripheral blood B cell subsets in MDR-TB and suggest that such changes should be taken into account when designing new strategies to boost the cellular and humoral immune response against Mtb.
Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marques de Pombal, 3004-517, Coimbra, Portugal.
Mónica T
MT
Abreu
Helena
H
Carvalheiro
Tiago
T
Rodrigues-Sousa
António
A
Domingos
António
A
Segorbe-Luis
Paulo
P
Rodrigues-Santos
M Margarida
MM
Souto-Carneiro
D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D037181:Lectins, C-Type / Q000032:analysis; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology* / Q000302:isolation & purification; D051217:Toll-Like Receptor 9 / Q000032:analysis; D018088:Tuberculosis, Multidrug-Resistant / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis; D000099192:CD69 Antigens
D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007072:Immunoglobulin D; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051217:Toll-Like Receptor 9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000099192:CD69 Antigens; C495371:TLR9 protein, human; C498154:CD38 protein, human