Abstract
BackgroundNumerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs. The aim of this study was to clarify whether specific IgE production is triggered by low antigen doses administrated in tertiary tissues enriched by lymphoid structures.MethodsOvalbumin (OVA) in different doses (100 ng to 10 μg) was administrated three times a week for 4–5 weeks intraperitoneally (i.p.) or subcutaneously (s.c.) to female BALB/c mice in the wither region which is enriched in fat-associated lymphoid clusters or in the foot pad region not containing them.ResultsOVA-specific IgE was predominantly induced by low but not high antigen doses and only after immunization into the withers. IgE isotype switching was triggered exclusively in the withers adipose tissue but not in the regional lymph nodes while mature IgE expressing cells were observed both in the withers and lymph nodes. Anti-proliferative genotoxic stress inducing drugs shifted the balance from IgG1 towards IgE production.ConclusionsTertiary lymphoid structures possess unique environment where B-cell antibody isotype switching to IgE predominantly occurs. This phenomenon is partially explained by hampered proliferation of B-cells in these structures.
Highlights
Numerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs
We have previously shown that in young (1–8 years old) patients with allergy to house dust mite specific IgE production is not associated with specific IgG, IgG4 or IgA1 production [4] and may occur outside the germinal centers of secondary lymphoid organs (SLOs)
Low dose antigen administration in tertiary lymphoid structures (TLSs)-enriched, but not TLS-depleted, zone induces specific IgE production To reconstitute typical clinical situation in which allergens enter mucosal tissue over a long period, mice were repeatedly immunized s.c. with low (10 or 100 ng), intermediate (1 μg) or high (10 μg) antigen doses in the regions which are enriched in TLSs such as withers (s.c.w.) and peritoneal cavity (i.p) or lack them
Summary
Numerous data obtained by different research laboratories indicate that specific IgE production is triggered independently of specific IgG or IgA ones and so it is not linked to fully matured germinal centers formation in the secondary lymphoid organs. We have previously shown that in young (1–8 years old) patients with allergy to house dust mite specific IgE production is not associated with specific IgG, IgG4 or IgA1 production [4] and may occur outside the germinal centers of secondary lymphoid organs (SLOs). It can occur in the tertiary lymphoid structures (TLSs) or so-called tissue-associated lymphoid clusters. Type 2 innate lymphoid cells (ILC2) activated by tissue damage-induced cytokines interleukins (IL) 25, 33 or thymic stromal lymphopoetin (TSLP) [5], instead of T helper-2 cells, may act as the main producers of proallergic cytokines like IL-5, 13 [5] and, to a lesser extent, IL-4 [6], in TLSs during the early phases of immune response
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