Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis.

Area of Science:

• Immunology
• Hematopoiesis

Background:

• B lymphopoiesis arrests in rabbits by 2-4 months of age.
• Adipocytes in mice inhibit B lymphopoiesis by inducing inflammatory myeloid cells producing IL-1β.

Purpose of the Study:

• Characterize rabbit bone marrow (BM) after B lymphopoiesis arrest.
• Investigate the role of BM fat and myeloid cells in regulating B lymphopoiesis.

Main Methods:

• Analyzed rabbit BM for fat, myeloid cells (CD11b+), and inflammatory molecules (IL-1β, S100A9).
• Assessed the impact of BM fat, myeloid cells, and S100A9 on B lymphopoiesis and myelopoiesis in vitro.
• Utilized NLRP3 inflammasome inhibitor (glibenclamide) to assess its effect on adipocyte-induced myeloid cell production.

Main Results:

• Rabbit BM showed increased fat, CD11b+ myeloid cells, and elevated IL-1β and S100A9 expression.
• BM fat, myeloid cells, and S100A9 inhibited B lymphopoiesis and enhanced myelopoiesis in vitro.
• S100A9 acts on myeloid cells to promote inflammatory molecule release, including IL-1β.
• Glibenclamide restored B lymphopoiesis and reduced myeloid cell induction by adipocyte-conditioned medium.

Conclusions:

• Bone marrow fat creates an inflammatory microenvironment.
• Activated myeloid cells produce IL-1β and S100A9, negatively regulating B lymphopoiesis.
• Targeting the NLRP3 inflammasome pathway may restore B lymphopoiesis in conditions of BM fat accumulation.