Rescue of the mature B cell compartment in BAFF-deficient mice by treatment with recombinant Fc-BAFF.
BAFF deficiency in mice impairs B cell development beyond the transitional stage 1 in the spleen and thus severely reduces the size of follicular and marginal zone B cell compartments. Moreover, humoral immune responses in these mice are dramatically impaired. We now addressed the question whether the decrease in mature B cell numbers and the reduced humoral immune responses in BAFF-deficient mice could be overcome by the injection of recombinant BAFF. We therefore engineered a recombinant protein containing the human IgG1 Fc moiety fused to receptor-binding domain of human BAFF (Fc-BAFF). At 1 week after the second injection of this fusion protein a complete rescue of the marginal zone B cell compartment and a 50% rescue of the follicular B cell compartment was observed. Moreover these mice mounted a T cell-dependent humoral immune response indistinguishable from wild-type mice. By day 14 upon arrest of Fc-BAFF treatment mature B cell numbers in the blood dropped by 50%, indicating that the life span of mature B cells in the absence of BAFF is 14 days or less. Collectively these findings demonstrate that injection of Fc-BAFF in BAFF-deficient mice results in a temporary rescue of a functional mature B cell compartment.
Swee
Lee Kim
LK
Developmental and Molecular Immunology, Department of Biomedicine, University of Basel, Mattenstrasse 28, Basel, Switzerland.
Tardivel
Aubry
A
Schneider
Pascal
P
Rolink
Antonius
A
D000818:Animals; D000917:Antibody Formation; D053264:B-Cell Activating Factor / Q000008:administration & dosage* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation; D002470:Cell Survival; D018858:Germinal Center; D006801:Humans; D007114:Immunization; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011994:Recombinant Proteins