In vitro requirement for periostin in B lymphopoiesis

Area of Science:

• Immunology
• Developmental Biology
• Extracellular Matrix Biology

Background:

• B lymphopoiesis, the development of B lymphocytes, arrests in rabbits by 4 months of age.
• The molecular mechanisms underlying this developmental arrest are not fully understood.
• Periostin (Postn) expression, encoding an extracellular matrix protein, significantly decreases with age in rabbit bone marrow stromal cells.

Purpose of the Study:

• To investigate the role of periostin in B lymphopoiesis.
• To identify molecular factors contributing to the age-related arrest of B lymphopoiesis.

Main Methods:

• cDNA-representational difference analysis to identify age-related gene expression changes in bone marrow stromal cells.
• In vitro studies using OP9 cells with and without periostin expression to assess effects on B-cell development.
• RGD peptide inhibition to block periostin/α(v)β(3) interactions.
• Microarray analysis to determine gene expression profiles.
• In vivo studies using periostin-deficient (Postn(-/-)) mice.

Main Results:

• Periostin deficiency in vitro leads to increased cell death and decreased proliferation of B-lineage progenitors.
• Re-expression of periostin restored the capacity of stromal cells to support B-cell development.
• Inhibition of periostin/α(v)β(3) interaction markedly decreased B lymphopoiesis in vitro.
• Periostin deficiency resulted in decreased expression of key B-lymphopoietic factors, including IL-7 and CXCL12.
• Postn(-/-) mice exhibited normal numbers of B-cell progenitors in bone marrow, suggesting compensatory mechanisms in vivo.

Conclusions:

• Periostin plays a critical role in supporting B lymphopoiesis in vitro, likely by providing proliferative and survival signals to B-cell progenitors through interaction with α(v)β(3).
• The age-related decline in periostin expression in rabbits contributes to, but does not solely explain, the arrest of B lymphopoiesis.
• Compensatory mechanisms exist in vivo that maintain B-cell progenitor numbers despite periostin loss.