Immunization of Newborn Mice Accelerates the Architectural Maturation of Lymph Nodes, But AID-Dependent IgG Responses Are Still Delayed Compared to the Adult

Abstract

Lymph nodes (LNs) have evolved to maximize antigen (Ag) collection and presentation as well as lymphocyte proliferation and differentiation—processes that are spatially regulated by stromal cell subsets, including fibroblastic reticular cells (FRCs) and follicular dendritic cells (FDCs). Here, we showed that naïve neonatal mice have poorly organized LNs with few B and T cells and undetectable FDCs, whereas adult LNs have numerous B cells and large FDC networks. Interestingly, immunization on the day of birth accelerated B cell accumulation and T cell recruitment into follicles as well as FDC maturation and FRC organization in neonatal LNs. However, compared to adults, the formation of germinal centers was both delayed and reduced following immunization of neonatal mice. Although immunized neonates poorly expressed activation-induced cytidine deaminase (AID), they were able to produce Ag-specific IgGs, but with lower titers than adults. Interestingly, the Ag-specific IgM response in neonates was similar to that in adults. These results suggest that despite an accelerated structural maturation of LNs in neonates following vaccination, the B cell response is still delayed and reduced in its ability to isotype switch most likely due to poor AID expression. Of note, naïve pups born to Ag-immunized mothers had high titers of Ag-specific IgGs from day 0 (at birth). These transferred antibodies confirm a mother-derived coverage to neonates for Ags to which mothers (and most likely neonates) are exposed, thus protecting the neonates while they produce their own antibodies. Finally, the type of Ag used in this study and the results obtained also indicate that T cell help would be operating at this stage of life. Thus, neonatal immune system might not be intrinsically immature but rather evolutionary adapted to cope with Ags at birth.

Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice

“…Although CAF01 can elicit fully established GCs in neonates (30) its effect on neonatal FDC-M2 + FDC maturation has not been reported. Others have proposed the role of FDC-M1 + FDCs (56, 57) and CR1 (56, 58) in the organization of B cell follicles and maintenance of GC in early life, whereas our previous work did not indicate that they were limiting factors for FDC network maturation (9). In agreement with our results, i.p.…”

Serratia symbiotica Enhances Fatty Acid Metabolism of Pea Aphid to Promote Host Development

“…It was speculated that acetate could be released into the host hemolymph and delivered into fat body cells as substrates for fatty acid synthesis. It has been extensively studied that some short-chain fatty acids, including acetate, produced by intestinal symbiotic bacteria can regulate the fatty acids synthesis of the mammalian host [ 37 ], but more details need to be determined about how facultative endosymbionts synthesize short-chain fatty acids in aphids. Furthermore, we also found that lipogenesis genes were highly expressed in the fat body, suggesting that peripheral sheath cells of the bacteriomes where Serratia is located may interact with the scattered fat body cells in the aphid hemolymph.…”

Understanding Antibody Responses in Early Life: Baby Steps towards Developing an Effective Influenza Vaccine

“…GC development requires structural organization by a network of follicular dendritic cells (FDCs) and follicular reticular cells (FRC), which are not fully mature during the early postnatal period [ 61 , 62 ]. The hampered ability to organize the anatomic architecture required for a GC reaction appears to not only delay the onset, but also limit persistence and diminish the magnitude of affinity matured antibody responses in newborn mice [ 63 ]. FDC immaturity is also associated with diminished availability of captured and displayed immune complexes in the GC, further limiting the capacity of B cells to take up and present antigen to acquire T cell help.…”