The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation

• Germinal center (GC) formation and antibody production in lymph node follicles require coordinated interactions between B-cells, T-cells and dendritic cells (DCs), orchestrated by the extracellular matrix-rich reticular fiber (RF) network. We describe a unique laminin 523-containing RF network around and between follicles that associates with PDGFrecb(high) CCL19(low)gp38(low) fibroblastic reticular cells (FRC). In the absence of FRC expression of laminin alpha 5 (pdgfrb-cre:Lama5(fl/fl)), pre-Tfh-cells, B-cells and DCs are displaced from follicle borders, correlating with fewer Tfh-cells and GC B-cells. Total DCs are not altered in pdgfrb-cre: Lama5(fl/fl) mice, but cDC2s, which localize to laminin alpha 5 in RFs at follicle borders, are reduced. In addition, PDGFrecb(high)CCL19(low)gp38(low) FRCs show lower Ch25h expression, required for 7 alpha,25-dihydroxycholesterol synthesis that attracts pre-Tfh-cells, B-cells and DCs to follicle borders. We propose that RF basement membrane components represent a type of tissue memory that guides the localization and differentiation of both specialized FRC and DC populations, required for normal lymph node function.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)