Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

Table 2

Possible impact of established and emerging therapies for MS on B cell function.

Therapeutic agent	Description	Impact on B-T interactions
Tysabri	Blocking antibody to α4β1 integrin (VLA4)	VLA4 is required for extravasation of lymphocytes across the blood brain barrier (BBB). A blockade of this adhesion molecule prevents autoreactive B and T cells from entering the CNS, thus limiting immune-mediated damage. CNS antigens are less available for antigen presentation without migration of antigen presenting cells (such as B cells) across the BBB.
MLN1202	CCR2 blocking antibody	Both B and T cells express CCR2, the receptor for MCP-1 [127]. Mouse studies show that MCP-1 is expressed in the microvessels [128] and that it is increased in MS [129]. This blocking antibody may abrogate leukocyte entrance into the CNS.
BAF312 and Fingolimod	blocking antibodies for the S1P receptor	These agents block egress of lymphocytes from secondary lymphoid organs. This therapy should decrease lymphocytes entry into the CNS. This mechanism is presumed to be similar to Tysabri.
Vitamin D3	Nutritional and environmental nutrient	The vitamin D3 receptor is expressed on GC and naïve and memory B cells [130]. Furthermore, Vitamin D3 reduces proliferative responses of B cells, reduces antibody secretion and class switching, inhibits maturation into memory and plasma phenotypes and induces apoptosis, but does not modulate the expression of HLA-DR or coreceptors [131]. Given these results, this therapy may have a profound effect on B cell activity in the context of MS.
CGP77116	Altered peptide ligand/mimetope for a dominant antigenic determinant of MBP (83–99)	CGP7716 will dampen the MBP-specific response by competing with native MBP. MBP-specific B cells could take up the APL and present it to T cells.
Glatiramer acetate (GA, Cop1, Copaxone)	Random polymer comprised of amino acids in a similar ratio as MBP	GA is known to skew the cytokine milieu toward a Th2 phenotype [132]. The effect of GA on B cell function is unknown.