To review the literature and discuss a hypothesis as to why most people do not become allergic. This hypothesis is dependent upon three main components. (1) Airborne allergens (for example from pollen or mites) are weak antigens that induce a B-cell response only in immunologically most reactive subjects (i.e., atopic). (2) A roadblock to production of IgE is the TH2/IL-4 requirement for class switch to IgE. (3) Activated germinal centers prevent the formation of mature IgE-switched B-cells, creating a second roadblock to IgE production.
Transgenic reporter mice and a cross-sectional human cohort.
From the mouse studies we selected the data on histology and tissue-derived cell suspensions published by several groups in 2011-2014. From the human cohort we selected our published micro-array data on the levels of allergenspecific IgE and IgG in serum.
The immune response to airborne atopic allergens entails both IgE and IgG antibodies rather than just an IgG or IgE response. However, as expected for an immune response without mature germinal centers, the specific IgG levels will be very low, typically in the ng/ml range.
Control of IgE production is not just through TH2/IL-4 mediated class switch. Recent studies suggest that mature germinal centers are likely to provide protection against the development of allergy to airborne allergens, as well. This may explain why allergen exposure does not induce allergen-specific IgE in everyone.
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Do germinal centers protect most of us from becoming allergic?
