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May 2006

Characterizing the Mechanisms and Progression in Multiple Sclerosis: Evidence and New Hypotheses for Future Directions—Reply

Arch Neurol. 2006;63(5):787-788. doi:10.1001/archneur.63.5.787

In reply

The focus of our review was not to instigate debate regarding the exact anatomical location of B cells within the CNS. Thus, we had globally referred to B cells as residing in the CNS to include any possible anatomical scenario, including the cerebrospinal fluid. Nevertheless, data from Serafini et al1 regarding the presence of CD138+ plasma cells in the brain parenchyma of even 1 patient brain with MS are relevant. For example, historically, B cells and plasma cells have only been observed in perivascular spaces, and not in the parenchyma,2 and in association with active lesions, not chronic inactive ones. However, Serafini et al1 observed that numerous CD20+ B cells had accumulated perivascularly in chronic inactive lesions and in the subarachnoid space, although not in the chronic active lesions themselves or demyelinated parenchyma. In contrast, plasma cells (identified as CD138+) were observed in parenchymal and meningeal blood vessels as well as within the parenchyma of chronic inactive lesions themselves. These observations suggest that B cells and plasma cells can be found in the parenchyma and in association with chronic inactive lesions, although this may not be a common event. Interestingly, these observations were made on samples taken from secondary progressive MS patients with the most severe demyelinating scores and in which intrameningeal follicles had been observed (2 of 3 examined). No B cells or plasma cells could be found in the secondary progressive MS brain specimen in which intrameningeal follicles could not be identified. In addition, while it is appropriate to emphasize that these data are somewhat limited, several factors, such as the difficulty in maintaining the integrity of the meninges during tissue processing and the scattered distribution of follicles throughout the specimens, make it difficult at best to generate a comprehensive database that would satisfy even the mildest critic.

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