Gustafson C E, Higbee D, Yeckes A R, Wilson C C, De Zoeten E F, Jedlicka P, Janoff E N
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.
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.
Mucosal Immunol. 2014 May;7(3):467-77. doi: 10.1038/mi.2013.64. Epub 2013 Sep 18.
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.
肠道中缺乏免疫球蛋白A（IgA）使幼儿极易受到肠道感染。然而，这一人群中初始IgA诱导的介质尚不清楚。我们确定了人类婴儿早期肠道中浆细胞按同种型的时间获得情况以及T细胞非依赖性（TI）和依赖性（TD）IgA类别转换因子的表达。我们发现，在1月龄之前，婴儿肠道中基本上没有IgA浆细胞，在婴儿期后期达到成人密度的时间比IgM和IgG都晚。第一个月IgA浆细胞的发育受限伴随着TI因子增殖诱导配体（APRIL）及其受体跨膜激活剂和钙调蛋白环孢素配体相互作用分子（TACI）以及孤立淋巴滤泡（ILF）内的B细胞成熟抗原（BCMA）表达降低。此外，随着时间的推移，APRIL和BCMA的表达均与IgA浆细胞密度的增加密切相关。相反，TD介质（CD40配体（CD40L）和CD40）在1月龄前就在ILF内表达，且与IgA浆细胞生成无关。此外，与足月儿相比，早产儿的IgA浆细胞密度较低且APRIL表达降低。因此，TI反应减弱可能导致人类婴儿早期肠道IgA诱导延迟。
