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NF-kB Activation by CD40 Is Increased in B Cells of Patients with Multiple Sclerosis: A Possible Target of Immunotherapy

Feb 3, 2017 11:26:40 AM / by Stacy Matthews Branch, DVM, PhD

Researchers used PBMCs to understand why patients with multiple sclerosis have hyperactive responses to CD40.An aspect of immunity involves the function of B lymphocytes (or B cells) that secrete antibodies. A protein expressed on B cells and other immune cells (CD40) is crucial for normal B cell action. CD40 interacts with a protein (CD40L) present on T cells that also contributes to B cell stimulation. This CD40-CD40L interaction is important for normal immune function. However, exaggerated B-cell responses to CD40 occur in autoimmune diseases such as multiple sclerosis. It has been shown that B cells from patients with relapsing-remitting multiple sclerosis (RRMS) are stimulated by CD40 to multiply significantly more than in healthy patients.

Recent research was conducted to understand why patients with MS have hyperactive responses to CD40. The researchers studied whether signals that are activated after CD40 action on B cells are also hyperactive. To do this, they collected peripheral blood mononuclear cells (PBMCs) from patients with and without RRMS before and after immunotherapy treatment. The PBMCs were prepared from leukapheresis packs from HemaCare, and phosphorylation (affecting function) of important cell signaling components (NF-kB and three major MAPKs) downstream of the CD40 B-cell interaction was analyzed.

The results showed that B cells had higher levels of NF-kB phosphorylation (but not of the MAPKs) after CD40 stimulation of total PBMCs taken from patients with RRMS. The researchers also observed that combination immunotherapy [with IFN-b-1a (Avonex) and mycophenolate mofetil (Cellcept)] lead to NF-kB phosphorylation levels that were similar to those of patients without MS. This change in phosphorylation level was also related to a lower disease activity.

These results suggest that some immunotherapies for MS may work by decreasing the stimulation of NF-kB that occurs due to CD40 activity. Studies are ongoing that look into the degree to which hyperactive CD40 responses contribute to the MS disease state and how current immunotherapies correct the impairment of CD40 action on B cells in patients with RRMS.

Are you interested in performing your own research? Contact HemaCare online or call 877-397-3087 to speak to a specialist or order your own supply of PBMCs.

Chen, Ding et al. "CD40-Mediated NF-Κb Activation In B Cells Is Increased In Multiple Sclerosis And Modulated By Therapeutics". The Journal of Immunology. N.p., 2017. Web. 26 Jan. 2017.

Topics: Autoimmune Disorders, PBMCs, stem cell research

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