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B-Crystallin, a Candidate Autoantigen in Multiple Sclerosis1
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands
The development of multiple sclerosis is most likely influenced by
autoimmune responses to central nervous system myelin proteins as well
as by infections with common viruses such as EBV and human
herpesvirus-6. However, much remains to be established on how these
factors interact. In this study, we show that upon EBV infection, human
B cells start to express 
B-crystallin, a small stress protein that
was identified previously as an immunodominant Ag of CNS myelin in
multiple sclerosis patients. EBV-induced expression of B-crystallin
in B cells leads to HLA-DR-restricted presentation of the protein and
to activation of proinflammatory B-crystallin-specific Th cells.
While B-crystallin is present in EBV-infected human B cells, the
protein is absent from human lymphoid tissues under normal conditions.
This is in sharp contrast to other stress proteins such as heat-shock
protein (hsp)27 and hsp60 that are ubiquitously expressed in these
tissues. In addition, the absence of B-crystallin from lymphoid
tissues in humans is unique as compared with other mammals. All other
species examined, including rodents, sheep, and primates, showed
constitutive expression of B-crystallin in secondary lymphoid
tissues and sometimes even in the thymus. Since constitutive lymphoid
expression most likely results in immunologic tolerance, such a state
of tolerance to B-crystallin can be expected for all of these
species, but not for humans. When taken together, our data provide
evidence for a novel mechanism by which common viral infections can
trigger myelin-directed autoimmunity in a way that is unique for
humans.
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