B Cell Memory in xid Mice is Long‐Lived Despite Reduced Memory B Cell Frequency

Abstract

Ridderstad A, Tarlinton DM. B Cell Memory in xid Mice is Long-Lived Despite Reduced Memory B Cell Frequency. Scand J Immunol 1997;45:655-659 Brutons tyrosine kinase (Btk) deficient xid mice have a diminished primary T cell dependent immune response, resulting in a reduced memory B cell frequency. Boosting at 35 days post primary immunization, however, generates a normal secondary immune response, indicating a functional memory B cell compartment. The longevity of B cell memory appears to depend on both the presence of antigen and expression of cell survival genes such as bcl-2. Since there is a natural decay in the number of memory B cells over time and since xid B cells have been demonstrated to have reduced Bcl-2 levels, we aimed at determining whether B cell memory of xid mice would be long-lasting. This report demonstrates that memory B cell precursors are detectable in xid mice more than 100 days after primary immunization. Furthermore, a secondary immune response of normal magnitude and kinetics can be generated in xid mice at 150 days after primary immunization indicating that B cell memory is long-lived in xid mice. Thus, although survival of B cell memory is presumably dependent on immunoglobulin (Ig)-mediated interaction with antigen, this interaction does not depend solely on signalling through Btk.

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

“…Given this premise, it is noteworthy that iMB cells are induced in vitro and develop in vivo in the absence of antigenic stimulation through the BCR. Th is indicates that, apart from its function for Ag presentation to T cells, BCR signalling per se is not necessary for GC B cells to become B mem cells, in agreement with studies showing a suffi cient memory recall response in Btk-and BLNK-defi cient mice 54,55 . It is also an intriguing fi nding that no specifi c GC microenvironment is required for B mem cell development, because the recipient mice do not develop GC.…”

NGF Withdrawal Induces Apoptosis in CESS B Cell Line through p38 MAPK Activation and Bcl-2 Phosphorylation

“…Amongst these, we selected the CESS cell line, which is an EBV-transformed EBNA ϩ cell line, that displays a CD19 ϩ , CD20 Ϫ , CD44 ϩ CD38 ϩ , CD77 Ϫ , IgGk ϩ surface phenotype, as assessed by a cytofluorimetric analysis performed with a panel of monoclonal antibodies. The class of membrane Ig receptors is consistent with the hypothesis that the normal cell originating this cell line was an antigen-selected, somatically hypermutated, proliferating B lymphocyte, a stage ontogenetically close to that of memory B cell (17).…”

Nerve Growth Factor-dependent Survival of CESS B Cell Line Is Mediated by Increased Expression and Decreased Degradation of MAPK Phosphatase 1

“…The lymphoblastoid CESS B cell line displays a CD19 ϩ , CD20 Ϫ , CD44 ϩ , CD38 ϩ , CD77 Ϫ , and IgGK ϩ surface phenotype (1), which suggests its origin from an antigen-selected, somatically hypermutated, and proliferating B lymphocyte, a stage ontogenetically close to that of memory B cells (2). Similar to memory B lymphocytes, CESS cells express both high affinity (p140 Trk-A ) and low affinity (p75 NTR ) NGF 1 receptors, spontaneously produce high amounts of NGF, and utilize it for their own survival (1,3).…”

“…Bcl-2 phosphorylation, which occurs in serine and threonine residues located in a loop between ␣1 and ␣2 helices (11), has been reported both as increasing or decreasing the anti-apoptotic potential of the protein (15). However, in memory B lymphocytes and in CESS cells, p38 MAPK-induced Bcl-2 phosphorylation, which occurs in Ser 87 and Thr 56 residues of the loop, (4), 2 causes cytochrome c release from mitochondria, caspase activation, and apoptotic death. In contrast, the addition of exogenous NGF induces dephosphorylation of p38 MAPK, which prevents Bcl-2 phosphorylation and cell apoptosis.…”