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PMID: 8976182 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice.

The Journal of experimental medicine ·Vol. 184 ·No. 6 ·1996-12-01 ·Pages 2271-8

Wolf SD, Dittel BN, Hardardottir F, Janeway CA

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an animal model for autoimmune central nervous system disease mediated by CD4 T cells. To examine the role of B cells in the induction of EAE, we used B10.PL (I-Au) mice rendered deficient in B cells by deletion of their mu chain transmembrane region (B10.PLmicroMT). By immunizing B10.PL and B10.PLmicroMT mice with the NH-terminal myelin basic protein encephalitogenic peptide Ac1-11, we observed no difference in the onset or severity of disease in the absence of mature B cells. There was, however, a greater variation in disease onset, severity, and especially of recovery in the B cell-deficient mice compared to controls. B10.PLmicroMT mice rarely returned to normal in the absence of B cells. Taken together, our data suggest that B cells do not play a role in the activation of encephalitogenic T cells, but may contribute to the immune modulation of acute EAE. The mechanisms to explain these effects are discussed.

MeSH Terms
Amino Acid Sequence Animals B-Lymphocytes/immunology Base Sequence Cytokines/biosynthesis DNA Primers Encephalomyelitis, Autoimmune, Experimental/immunology Flow Cytometry Immunoglobulin mu-Chains/genetics Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Mutant Strains Molecular Sequence Data Peptide Fragments/chemical synthesis,immunology Polymerase Chain Reaction RNA, Messenger/biosynthesis Sequence Deletion T-Lymphocytes/immunology Transcription, Genetic
Chemicals
Cytokines DNA Primers Immunoglobulin mu-Chains Peptide Fragments RNA, Messenger
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Wolf S D
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Dittel B N
Hardardottir F
Janeway C A
References (53)
53 references, click to expand
  1. Regulation of antigen-presentation-I. IFN-gamma induces antigen-presenting properties on B cells.
    J Immunol. 1988 Dec 15;141(12):4083-8 PMID: 2974053
  2. Distinct features of dendritic cells and anti-Ig activated B cells as stimulators of the primary mixed leukocyte reaction.
    J Exp Med. 1989 Jan 1;169(1):239-54 PMID: 2562848
  3. Control of the immune response at the level of antigen-presenting cells: a comparison of the function of dendritic cells and B lymphocytes.
    Adv Immunol. 1989;47:45-116 PMID: 2554698
  4. Induction of autoreactive B cells allows priming of autoreactive T cells.
    J Exp Med. 1991 Jun 1;173(6):1433-9 PMID: 1851798
  5. Microbial induction of co-stimulatory activity for CD4 T-cell growth.
    Int Immunol. 1991 Apr;3(4):323-32 PMID: 1831651
  6. Strong priming of T cells adoptively transferred into scid mice.
    J Exp Med. 1991 Dec 1;174(6):1653-6 PMID: 1744589
  7. Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens.
    J Exp Med. 1992 Jan 1;175(1):131-8 PMID: 1730913
  8. Antigen-pulsed dendritic cells can efficiently induce an antibody response in vivo.
    J Exp Med. 1992 Jan 1;175(1):15-21 PMID: 1370527
  9. Targeted disruption of mu chain membrane exon causes loss of heavy-chain allelic exclusion.
    Nature. 1992 Mar 12;356(6365):154-6 PMID: 1545868
  10. Immunological aspects of demyelinating diseases.
    Annu Rev Immunol. 1992;10:153-87 PMID: 1375472
  11. B cells turn off virgin but not memory T cells.
    Science. 1992 Nov 13;258(5085):1156-9 PMID: 1439825
  12. Synergy between encephalitogenic T cells and myelin basic protein-specific antibodies in the induction of experimental autoimmune encephalomyelitis.
    J Neuroimmunol. 1992 Nov;41(1):1-8 PMID: 1281165
  13. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma.
    J Exp Med. 1993 Jan 1;177(1):57-68 PMID: 7678116
  14. B lymphocytes in vivo fail to prime naive T cells but can stimulate antigen-experienced T lymphocytes.
    J Exp Med. 1993 Mar 1;177(3):679-90 PMID: 8436906
  15. The involvement of T cell receptor peptide-specific regulatory CD4+ T cells in recovery from antigen-induced autoimmune disease.
    J Exp Med. 1993 Sep 1;178(3):909-16 PMID: 7688792
  16. Altered response of CD4+ T cell subsets to Plasmodium chabaudi chabaudi in B cell-deficient mice.
    Int Immunol. 1993 Oct;5(10):1343-8 PMID: 8268139
  17. Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity.
    J Exp Med. 1994 Feb 1;179(2):589-600 PMID: 7905019
  18. In vivo activation of naive T cells by antigen-presenting B cells.
    J Immunol. 1994 Apr 15;152(8):3777-85 PMID: 8144947
  19. Antigen-specific activation, tolerization, and reactivation of the interleukin 4 pathway in vivo.
    J Exp Med. 1994 Jun 1;179(6):1885-93 PMID: 7910842
  20. A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation.
    J Exp Med. 1994 Nov 1;180(5):1829-40 PMID: 7525839
  21. Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.
    J Exp Med. 1994 Nov 1;180(5):1961-6 PMID: 7525845
  22. B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy.
    Cell. 1995 Mar 10;80(5):707-18 PMID: 7534215
  23. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo.
    J Exp Med. 1995 Apr 1;181(4):1569-74 PMID: 7699337
  24. Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines.
    J Immunol. 1995 May 1;154(9):4269-82 PMID: 7536767
  25. Immunological aspects of experimental allergic encephalomyelitis and multiple sclerosis.
    Crit Rev Clin Lab Sci. 1995;32(2):121-82 PMID: 7598789
  26. Relationships among antigen presentation, cytokines, immune deviation, and autoimmune disease.
    J Exp Med. 1995 Aug 1;182(2):279-82 PMID: 7543132
  27. Prevention of experimental allergic encephalomyelitis in rats by targeting autoantigen to B cells: evidence that the protective mechanism depends on changes in the cytokine response and migratory properties of the autoantigen-specific T cells.
    J Exp Med. 1995 Aug 1;182(2):335-44 PMID: 7543135
  28. Antigen-specific interaction between T and B cells.
    Nature. 1985 Apr 11-17;314(6011):537-9 PMID: 3157869
  29. Antigen presentation by splenic B cells: resting B cells are ineffective, whereas activated B cells are effective accessory cells for T cell responses.
    J Immunol. 1985 Nov;135(5):2937-45 PMID: 2413104
  30. T cell development in B cell-deficient mice. IV. The role of B cells as antigen-presenting cells in vivo.
    J Immunol. 1986 Feb 1;136(3):823-9 PMID: 2416835
  31. Immunoglobulin deficient rats as donors and recipients of effector cells of allergic encephalomyelitis.
    J Neuroimmunol. 1986 Apr;11(2):93-103 PMID: 2419359
  32. The B cell is the initiating antigen-presenting cell in peripheral lymph nodes.
    J Immunol. 1987 Feb 15;138(4):1051-5 PMID: 3100626
  33. The role of antigen-presenting B cells in T cell priming in vivo. Studies of B cell-deficient mice.
    J Immunol. 1988 Jun 1;140(11):3773-8 PMID: 2453554
  34. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention.
    Cell. 1988 Jul 15;54(2):263-73 PMID: 2455603
  35. Can B cells turn on virgin T cells?
    Nature. 1988 Jul 21;334(6179):253-5 PMID: 2969460
  36. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy.
    Cell. 1988 Aug 12;54(4):577-92 PMID: 2456857
  37. B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells to protein antigens in vivo.
    J Immunol. 1995 Oct 15;155(8):3734-41 PMID: 7561077
  38. Successful T cell priming in B cell-deficient mice.
    J Exp Med. 1995 Oct 1;182(4):915-22 PMID: 7561694
  39. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
    J Exp Med. 1995 Dec 1;182(6):1985-96 PMID: 7500044
  40. Dendritic cells but not B cells present antigenic complexes to class II-restricted T cells after administration of protein in adjuvant.
    J Exp Med. 1996 Mar 1;183(3):751-7 PMID: 8642279
  41. B cells solicit their own help from T cells.
    J Exp Med. 1996 Mar 1;183(3):891-9 PMID: 8642293
  42. CD4+ T cell activation and tolerance induction in B cell knockout mice.
    J Exp Med. 1996 Apr 1;183(4):1339-44 PMID: 8666892
  43. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis.
    Eur J Immunol. 1981 Mar;11(3):195-9 PMID: 6165588
  44. Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice.
    Eur J Immunol. 1981 Dec;11(12):964-8 PMID: 6173237
  45. Immunoglobulin-deficient rats fail to develop experimental allergic encephalomyelitis.
    J Neuroimmunol. 1983 Oct;5(2):99-109 PMID: 6194180
  46. Cutaneous leishmaniasis in anti-IgM-treated mice: enhanced resistance due to functional depletion of a B cell-dependent T cell involved in the suppressor pathway.
    J Immunol. 1984 Apr;132(4):2072-7 PMID: 6230400
  47. Resting and sensitized T lymphocytes exhibit distinct stimulatory (antigen-presenting cell) requirements for growth and lymphokine release.
    J Exp Med. 1984 Dec 1;160(6):1717-35 PMID: 6239901
  48. Major histocompatibility complex-linked control of the murine immune response to myelin basic protein.
    J Immunol. 1985 Apr;134(4):2328-32 PMID: 2579140
  49. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
    J Exp Med. 1989 Dec 1;170(6):2081-95 PMID: 2531194
  50. Regulation of T-cell activation: differences among T-cell subsets.
    Immunol Rev. 1989 Oct;111:79-110 PMID: 2534116
  51. The T lymphocyte in experimental allergic encephalomyelitis.
    Annu Rev Immunol. 1990;8:579-621 PMID: 2188675
  52. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ.
    J Exp Med. 1990 Aug 1;172(2):631-40 PMID: 2373994
  53. A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene.
    Nature. 1991 Apr 4;350(6317):423-6 PMID: 1901381
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1996-12-01
Pages
2271-8
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196394
Subset
IM
Grants
NIAID NIH HHS · AI-36529 · United States
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