Unique ErkMAPkinase checkpoint signatures drive differential responses during the immature-mature B cell transition?

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B-lymphocytes are cells that produce proteins known as antibodies that play important roles in the body s fight against infection. In order to fight any infection, vast numbers of randomly different B cells are made. However, many of these B cells can potentially make antibodies capable of attacking molecules within the body (self molecules), resulting in autoimmune diseases like Rheumatoid Arthritis. The immune system has therefore evolved checkpoints to prevent production of autoimmune B cells by killing immature cells that attach themselves to self molecules in a process known as tolerance. By contrast, when mature tolerant B cells encounter infections, many of these B cells develop into antibody-secreting cells to fight the disease. In addition, some become memory B cells that can produce faster, better antibody responses if the host becomes re-infected with this same disease. ?Memory? is the basis underlying the development of vaccines against diseases such as tetanus and polio. The aim of this application, therefore, is to work out the key molecular events regulating destruction of autoreactive B cells and retention of useful B cell specificities as identification of these has obvious potential for the development of new vaccine, cancer and autoimmunity therapies.