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