AdvisorCerny, Jan, 1939-
MetadataShow full item record
AbstractMarginal zone (MZ) B cells are the major cell population in the spleen to respond to T-independent type II antigens (Ti-II) in the blood. However, the evidence regarding the potential role of MZ B cells in response to T-dependent Ag (Td-Ag) is still rudimentary and somewhat controversial, as studies with Pyk-2-/- and RBP-J conditional deficient mice showed opposite results. The current study compared in detail, the responses of MZ and follicular (FO) B cell to a Td Ag, Nitrophenyl-hapten (NP) coupled to chicken gamma globulin (NP-CGG) in an adoptive transfer experiment. The results showed that MZ B cells are the major population to generate early antibody-forming cells (AFC) and they produce about 10-fold higher IgM and slightly higher IgG throughout the entire primary response observed (3 months) compared to FO B cells. In addition, MZ B cells gave rise to germinal center (GC) formation albeit with a delayed onset. GCs from both MZ and FO B cells displayed similar levels of somatic hypermutation (SHM) frequencies, clonal selection, and IgG memory responses. Surprisingly, MZ B cells also produced an IgM memory response. The VH gene repertoire of the early antibody forming cells (AFCs) from MZ B cells is different from that of GCs and late AFCs, suggesting their origins from different precursors. Studies on gene expression profile showed that MZ B cells express some early activation markers both on cell surface, such as B7-2, CD54, and CD44, and intracellularly, such as c-myc, pim-1, and fos proteins, consistent with their rapid response to stimulation. Most importantly, MZ B cells upregulate gene expression of the Blimp-1, which confers MZ B cells the propensity to rapidly develop into plasma cells. In addition, MZ B cells differentially express higher levels of RP105, a LPS receptor on B cells, which may explain the stronger response of MZ B cells to LPS stimulation and the predominant role in Ti responses. In conclusion, MZ B cells are phenotypically and functionally heterogeneous and they have the potential to respond to both Ti and Td Ags.
DescriptionUniversity of Maryland, Baltimore. Microbiology and Immunology. Ph.D. 2003
Health Sciences, Immunology
Lymphoma, B-Cell, Marginal Zone--immunology