Dual role of B cells with accelerated onset but reduced disease activity in P0₁₀₆₋₁₂₅-induced experimental autoimmune neuritis of IgH ⁰(/)⁰ mice.
The role of B cells in autoimmune-mediated diseases of the peripheral nervous system was studied in experimental autoimmune neuritis (EAN) in B cell deficient IgH⁰(/)⁰ C57BL/6J mice having been immunized with P0₁₀₆₋₁₂₅ peptide. Compared to coisogenic IgH(+/+) mice, onset of EAN was accelerated [100% disease incidence at day 9 post immunization (p.i.) vs. day 15 p.i.]. At day 9 p.i., numbers of P0₁₀₆₋₁₂₅-specific interferon (IFN)-γ-producing CD4(+) T cells were increased, while IL-10 mRNA and production were decreased in IgH⁰(/)⁰ mice. Beyond day 9 p.i., declining disease activity and a significant reduction of maximal disease activity were correlated with significantly reduced numbers of IFN-γ-producing CD4(+) T cells in IgH(0/0) mice as compared with IgH(+/+) mice. Correspondingly, neuropathology demonstrated only mild axonal damage, while demyelination and dying back axonopathy with spinal cord motor neuron apoptosis were absent. Thus, depending on the stage of EAN, B cells play a dual, i.e. suppressive and enhancing, role during induction and at height of EAN, respectively. The combined interaction of B cells as well as CD4(+) and CD8(+) T cells is required for the development of EAN.
Brunn
Anna
A
Department of Neuropathology, University Hospital of Cologne, Germany. anna.brunn@uni-koeln.de
Utermöhlen
Olaf
O
Sánchez-Ruiz
Monica
M
Montesinos-Rongen
Manuel
M
Blau
Tobias
T
Schlüter
Dirk
D
Deckert
Martina
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D050438:Genes, Immunoglobulin Heavy Chain; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018993:Myelin P0 Protein / Q000276:immunology; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018993:Myelin P0 Protein; D016753:Interleukin-10; D007371:Interferon-gamma