Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF.
We previously demonstrated that in vitro stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes, class switch recombination (CSR), induction of the E2A-encoded transcription factor E47, and activation-induced cytidine deaminase (AID) which is necessary for CSR and somatic hypermutation. Both anti-CD40 as well as BAFF have been shown to be able to induce CSR. We have investigated the ability of BAFF/IL-4, as compared to anti-CD40/IL-4, to induce CSR to gamma(1) in splenic B cells from young and old mice. We found that anti-CD40/IL-4 is a better CSR stimulus than BAFF/IL-4 in young B cells, as measured by RT-PCR of post-switch transcripts and flow cytometry. CSR is reduced in old B cells and this is independent of the stimulus. AID and gamma(1)PSTs are significantly reduced in old B cells stimulated with anti-CD40/IL-4, but only slightly reduced with BAFF/IL-4. BAFF receptor mRNA expression (BAFF-R, TACI, and BCMA) is not affected by aging. The age-related decrease in CSR induced by anti-CD40/IL-4 is primarily associated with a decrease in E47, whereas the less affected response to BAFF/IL-4 is associated with decreases in both E47 and NF-kappaB. Therefore, NF-kappaB is not involved in the decreased response of old B cells to anti-CD40/IL-4. These differences in B cell responses to CD40/IL-4 and BAFF/IL-4 may help to explain the maintenance of TI vs TD responses in senescent mice.
Frasca
Daniela
D
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Riley
Richard L
RL
Blomberg
Bonnie B
BB
D000375:Aging / Q000276:immunology*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D053264:B-Cell Activating Factor / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D053301:B-Cell Maturation Antigen / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000276:immunology; D005260:Female; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000276:immunology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000906:Antibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D019013:CD40 Antigens; D007074:Immunoglobulin G; D012333:RNA, Messenger; C490176:Tnfrsf17 protein, mouse; D014157:Transcription Factors; D053303:Transmembrane Activator and CAML Interactor Protein; D015847:Interleukin-4; D007073:Immunoglobulin E; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase