Abstract
Introduction: B cells are multifunctional leukocytes that act as regulators of allergic inflammation. They differentiate in the bone marrow (BM) from Haematopoietic Stem Cells via pro-B, pre-B and immature B cells. During airway challenge, effectors cells, i.e. eosinophils, move to the lung in different developmental stages implying local differentiation. It is still unclear if this also applies to B cells.
Aim: To determine the numbers and phenotypes of B cell precursors in the lung after allergen exposure and investigate their proliferation and activation status in situ.
Methods: Ovalbumin (OVA)-sensitized BALB/c mice were exposed intranasally to OVA or PBS for 5 days. Lung tissue was harvested 24h after final allergen exposure. Cells were stained for markers of B cell differentiation (B220, CD43, IL-7R, BP-1, IgM/IgD, IgE, CD138), chemotaxis (CXCR4), viability/proliferation/apoptosis (7AAD/BrdU/Bax) and direct/indirect activation (CD69/CD40,CD86).
Results: Pro-B (B220+/CD43+/BP-1-) and pre-B (B220+/CD43-/BP-1+) progenitors increased in the lung after allergen exposure, showed high rate of proliferation (BrdUhigh) and expressed CXCR4. Pro-B cells exhibited resistance to apoptosis (Bax downregulation), while pre-B cells showed increased expression of functional activation (CD40, CD86) and proliferation in situ (s+G2/M phase).
Conclusion: Allergen exposure promotes an influx of specific B cell precursor subsets in the lung with anti-apoptotic characteristics that can proliferate in-situ, migrate and be activated. Our data support the notion of a potential regulatory role of B cell precursors in allergic airway inflammation.
- © 2014 ERS