What if we could reconstruct the way B and T cells interact?

We know B and T cell interaction leads to CNS damage in MS, but we're just beginning to connect the dots of this complicated relationship.1

Exploring B and T cell crosstalk1-4

Lymphocytes have complex relationships and interactions with each other. The crosstalk between B and T cells seems to have a specific role in the pro-inflammatory cascade that is seen in MS.1-4

B cells stimulate T cells by:

  • Secretion of cytokines that bind and activate T cells
  • Ligand binding of T cell receptors

T cells stimulate B cells by:

  • Increasing B cell proliferation and survival
  • Increasing plasma cell differentiation
  • Increasing B cell adhesion to the blood-brain barrier

MS involves many different cells all working together and signaling each other in complex ways. To find the next big advancement in the treatment of MS, we want to understand these mechanisms.

Digging deeper into B and T cell
crosstalk in MS

Taking a closer look at
memory B and T cells

More recently, there is evidence that specific subsets of B and T cells—memory B cells and memory T cells—play a key role in MS.5

MEMORY B CELLS
Cells of the B cell lineage, including primarily memory B cells, are found to persist in the inflamed MS CNS6
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Depletion of memory B cells reduces MRI lesions and relapses7
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Memory B cells can be produced in the tertiary lymphoid organs of the CNS8
MEMORY T CELLS
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In MS patients, 84% of T cells reactive to a myelin protein were of the memory T cell subset9
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The numbers of certain circulating memory T cells were correlated positively with EDSS scores10
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Th1/Th17 central memory cells were found to be increased in patients with RMS with a high disease score after an MS attack5

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WHICH B AND T CELL INTERACTIONS IN MS DO YOU FIND MOST COMPELLING?2,5

(SELECT ONE)

POLL RESULTS

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Ligand mediated costimulation
Cytokine mediated responses
T cell mediation of increased plasma cell differentiation

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REFERENCES

1. Dalakas M. B cells as therapeutic targets in autoimmune neurological disorders. Nat Clin Pract Neurol. 2008;4(10):557-567. 2. Ireland S, Monson N. Potential impact of B cells on T cell function in multiple sclerosis. Mult Scler Int. 2011;2011: 423971. 3. Takemori T, Kaji T, Takahashi Y, Shimoda M, Rajewsky K. Generation of memory B cells inside and outside germinal centers. Eur J Immunol. 2014;44(5):1258-1264. 4. Pikor N, Prat A, Bar-Or A, Gommerman J. Meningeal tertiary lymphoid tissues and multiple sclerosis: a gathering place for diverse types of immune cells during CnS autoimmunity. Front Immunol. 2016;6:1-7. 5. Paroni M, Maltese V, De Simone M, et al. Recognition of viral and self-antigens by TH1 and TH1/TH17 central memory cells in patients with multiple sclerosis reveals distinct roles in immune surveillance and relapses. J Allergy Clin Immunol. 2017;140(3):797-808. 6. Baker D, Marta M, Pryce G, Giovannoni G, Schmierer K. Memory B cells are major targets for effective immunotherapy in relapsing multiple sclerosis. EBioMedicine. 2017;16:41-50. 7. Hauser S, Waubant E, Arnold D, et al. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med. 2008;358(7):676-688. 8. Mitsdoerffer M, Peters A. Tertiary lymphoid organs in central nervous system autoimmunity. Front Immunol. 2016;7:451:1-12. 9. Burns J, Bartholomew B, Lobo S. Isolation of myelin basic protein–specific T cells predominantly from the memory T‐cell compartment in multiple sclerosis. Ann Neurol. 1999;45(1):33-39. 10. Fan X, Jin T, Zhao S, Liu C, Han J, Jiang X. Circulating CCR7+ ICOS+ memory T follicular helper cells in patients with multiple sclerosis. PLoS One. 2015;10(7):e0134523.