title: Limited expression of APRIL and its receptors prior to intestinal IgA plasma cell development during human infancy.
abstract: The absence of immunoglobulin A (IgA) in the intestinal tract renders young infants highly susceptible to enteric infections. However, mediators of initial IgA induction in this population are undefined. We determined the temporal acquisition of plasma cells by isotype and expression of T cell-independent (TI) and -dependent (TD) IgA class switch factors in the human intestinal tract during early infancy. We found that IgA plasma cells were largely absent in the infant intestine until after 1 month of age, approaching adult densities later in infancy than both IgM and IgG. The restricted development of IgA plasma cells in the first month was accompanied by reduced expression of the TI factor a proliferation-inducing ligand (APRIL) and its receptors TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) and B cell maturation antigen (BCMA) within isolated lymphoid follicles (ILFs). Moreover, both APRIL and BCMA expression strongly correlated with increasing IgA plasma cell densities over time. Conversely, TD mediators (CD40 ligand (CD40L) and CD40) were expressed within ILFs before 1 month and were not associated with IgA plasma cell generation. In addition, preterm infants had lower densities of IgA plasma cells and reduced APRIL expression compared with full-term infants. Thus, blunted TI responses may contribute to the delayed induction of intestinal IgA during early human infancy.
authors.affiliation: 1] Mucosal and Vaccine Research Program Colorado (MAVRC), Infectious Disease Division, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [2] Integrated Department of Immunology, National Jewish Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [3] Department of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Gustafson
authors.affiliation: 1] Mucosal and Vaccine Research Program Colorado (MAVRC), Infectious Disease Division, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [2] Department of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors.forename: D
authors.initials: D
authors.lastname: Higbee
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Yeckes
authors.affiliation: 1] Mucosal and Vaccine Research Program Colorado (MAVRC), Infectious Disease Division, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [2] Integrated Department of Immunology, National Jewish Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: Wilson
authors.affiliation: Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: De Zoeten
authors.affiliation: Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: P
authors.initials: P
authors.lastname: Jedlicka
authors.affiliation: 1] Mucosal and Vaccine Research Program Colorado (MAVRC), Infectious Disease Division, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [2] Integrated Department of Immunology, National Jewish Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA [3] Department of Medicine, Denver Veterans Affairs Medical Center, Denver, Colorado, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Janoff
mesh_terms: D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D053301:B-Cell Maturation Antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
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