DOI: 10.4049/jimmunol.161.2.692. Antigen-Dependent Intrathecal Antibody Synthesis in the Normal Rat Brain: Tissue Entry and Local Retention of Antigen-Specific B Cells

Antigen-Dependent Intrathecal Antibody Synthesis in the Normal Rat Brain: Tissue Entry and Local Retention of Antigen-Specific B Cells

10.4049/jimmunol.161.2.692

Crossref journal-article

Oxford University Press (OUP)

The Journal of Immunology (286)

Abstract

Abstract The intrathecal Ab response to Ag introduced into the normal brain has not been fully explored. Involvement of Ag-specific, peripheral B cells in an intrathecal response was studied using a normal rat model of Ag infusion through an indwelling cannula into defined brain sites, while maintaining a functionally intact blood-brain barrier. Specific Ab was detected in serum and cerebrospinal fluid. The intrathecal response is first detectable at day 14. Isoelectric focusing of cerebrospinal 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 were preimmunized peripherally. Subsequently, Ag or saline (control) was infused through the cannula. Under this protocol, intrathecal synthesis is detectable earlier (day 5 postinfusion). Immunohistochemical studies at the infusion site assessed Ag-specific B cells, T cells, and activated APCs. Rats receiving peripheral preimmunization followed by Ag into caudate nucleus have far greater numbers of these cells, including plasma cells, within the infusion site compared with saline controls. Results confirm previous indirect evidence of intrathecal Ab synthesis in normal rat brain and provide the first direct evidence for B cell trafficking across normal brain barriers plus retention at the Ag deposition site. Our studies indicate that the normal brain microenvironment supports development of Ag-directed humoral immunity. We propose that immune privilege in normal brain is characterized by down-regulation of cell-mediated but not Ab immune responses within the central nervous system.

Bibliography

Knopf, P. M., Harling-Berg, C. J., Cserr, H. F., Basu, D., Sirulnick, E. J., Nolan, S. C., Park, J. T., Keir, G., Thompson, E. J., & Hickey, W. F. (1998). Antigen-Dependent Intrathecal Antibody Synthesis in the Normal Rat Brain: Tissue Entry and Local Retention of Antigen-Specific B Cells. The Journal of Immunology, 161(2), 692â701.

Authors 10

Paul M. Knopf (first)
Christine J. Harling-Berg (additional)
Helen F. Cserr (additional)
Devraj Basu (additional)
Erik J. Sirulnick (additional)
Scott C. Nolan (additional)
Joel T. Park (additional)
Geoffrey Keir (additional)
Edward J. Thompson (additional)
William F. Hickey (additional)

References 32 Referenced 159

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Cserr, H. F., P. M. Knopf. 1997. Cervical lymphatics, the blood-brain barrier, and immunoreactivity of the brain. R. W. Keane, and W. F. Hickey, eds. Immunology of the Nervous System 134 Oxford University Press, NY.
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Cserr, H. F., M. DePasquale, C. J. Harling-Berg, J. T. Park, P. M. Knopf. 1992. Afferent and efferent arms of the humoral immune response to CSF-administered albumins in a rat model with normal blood-brain barrier permeability. J. Neuroimmunol. 41: 195 (10.1016/0165-5728(92)90070-2)
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Dates

Type	When
Created	2 years, 8 months ago (Dec. 31, 2022, 9:19 a.m.)
Deposited	8 months ago (Jan. 2, 2025, 12:02 p.m.)
Indexed	1 week, 6 days ago (Aug. 23, 2025, 9:31 p.m.)
Issued	27 years, 1 month ago (July 15, 1998)
Published	27 years, 1 month ago (July 15, 1998)
Published Print	27 years, 1 month ago (July 15, 1998)

Funders 0

None

BibTeX

@article{Knopf_1998, title={Antigen-Dependent Intrathecal Antibody Synthesis in the Normal Rat Brain: Tissue Entry and Local Retention of Antigen-Specific B Cells}, volume={161}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.161.2.692}, DOI={10.4049/jimmunol.161.2.692}, number={2}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Knopf, Paul M. and Harling-Berg, Christine J. and Cserr, Helen F. and Basu, Devraj and Sirulnick, Erik J. and Nolan, Scott C. and Park, Joel T. and Keir, Geoffrey and Thompson, Edward J. and Hickey, William F.}, year={1998}, month=jul, pages={692–701} }

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