title: Transcriptional control of activation-induced cytidine deaminase and error-prone DNA polymerases is functionally mature in the B cells of infants at birth.
abstract: Somatic hypermutation (SHM) of immunoglobulin genes requires activation-induced cytidine deaminase (AID). The error-prone DNA polymerases, such as Pol eta, Pol zeta, and Pol iota, also have been implicated in the process. Human adult antibodies directed to microbial pathogens are increased in affinity and function compared with those of infants. Adult antibodies achieve this increased affinity through somatic mutations, which are lacking in the B cells of infants. It is unknown if infant B cells are capable of upregulating the cell machinery needed to introduce mutations after stimulation through the antigen receptor. We show here that infant B cells exhibit similar kinetics and magnitude of transcription of AID and pol eta genes and only marginally lower levels of pol iota and pol zeta genes after stimulation through the B cell receptor. These data suggest that the ability to upregulate gene transcription of enzymes mediating SHM is not a limiting determinant of the functional quality of infant antibody responses.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, TN 37232-2905, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Bowen
authors.forename: Cuixia
authors.initials: C
authors.lastname: Tian
authors.forename: Bonnie J
authors.initials: BJ
authors.lastname: LaFleur
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000201:enzymology*; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007231:Infant, Newborn; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D014158:Transcription, Genetic; D015854:Up-Regulation; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004259:DNA-Directed DNA Polymerase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase