ANTIGEN-DEPENDENT INTRATHECAL ANTIBODY-SYNTHESIS IN THE NORMAL RAT-BRAIN - TISSUE ENTRY AND LOCAL RETENTION OF ANTIGEN-SPECIFIC B-CELLS

The intrathecal Ab response to Ag introduced into the normal brain has not been fully explored. Involvement of Ag-specific, peripheral B cel ls in an intrathecal response was studied using a normal rat model of Ag infusion through are indwelling cannula into defined brain sites, w hile maintaining a functionally intact blood-brain barrier. Specific A b was detected in serum and cerebrospinal fluid. The intrathecal respo nse is first detectable at day 14. Isoelectric focusing of cerebrospin al fluid reveals banding patterns consistent with local Ab production. To increase Ag-specific, circulating peripheral lymphocytes available for trafficking to Ag-stimulated brain and for enhancing intrathecal Ab synthesis, rats mere preimmunized peripherally, Subsequently,, Ag o r saline (control) was infused through the cannula, Under this protoco l, intrathecal synthesis is detectable earlier (day 5 postinfusion), I mmunohistochemical studies at the infusion site assessed Ag-specific B cells, T cells, and activated APCs. Rats receiving peripheral preimmu nization followed by Ag into caudate nucleus have far greater numbers of these cells, including plasma cells, within the infusion site compa red with saline controls, Results confirm previous indirect evidence o f intrathecal Ab synthesis in normal rat, brain and provide the first direct evidence for B cell trafficking across normal brain barriers pl us retention at the Ag deposition site, Our studies indicate that the normal brain microenvironment supports development of Ag-directed humo ral immunity, We propose that immune privilege in normal brain is char acterized by down-regulation of cell-mediated but not Ab immune respon ses within the central nervous system.