Polyclonal B-cell expansion in the cerebrospinal fluid of patients with pseudotumor cerebri.
To investigate the hypothesis that pseudotumor cerebri (PTC) is associated with humoral immunity, we analyzed immunoglobulin heavy chain variable region (Ig-VH) genes of B cells in the cerebrospinal fluid (CSF) of 10 patients with PTC. Using RT-PCR and sequencing techniques, intrathecal B-cell Ig-VH genes were amplified in 6 of 10 PTC samples. Sequence analysis of complementarity-determining region 3 (CDR 3) and VH genes revealed a polyclonal intrathecal B-cell expansion in these patients. The nucleotide sequences showed that one-third of analyzed sequences had a high replacement to silent nucleotide substitution ratio, indicating an antigen-driven T-cell-dependent intrathecal B-cell proliferation. Moreover, other one-third had germline VH genes without or with a few nucleotide mutations, suggesting a T-cell-independent natural B-cell-mediated humoral immunity in the CNS of these patients. Our results suggest that both T-cell-dependent and T-cell-independent humoral immunity are present in the CSF of PTC.
Da
Reng-Rong
RR
Department of Neurology, University of California, Irvine, California 92697, USA.
Kao
Grace
G
Guo
Wen-Zhong
WZ
Olek
Michael
M
Gupta
Sudhir
S
Zhang
Yiping
Y
Van Den Noort
Stanley
S
Qin
Yufen
Y
D000293:Adolescent; D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D049109:Cell Proliferation; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology*; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011559:Pseudotumor Cerebri / Q000134:cerebrospinal fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology