Memory antibody responses are typically seen to T-cell-dependent antigens and are characterized by the rapid production of high titers of high-affinity antigen-specific antibody. The hallmark of T-cell-dependent memory B cells is their expression of a somatically mutated, isotype-switched B-cell antigen receptor, features that are mainly generated in germinal centers. Classical studies have focused on isotype-switched memory B cells (mainly IgG isotype) and demonstrated their unique intrinsic properties in terms of localization and responsiveness to antigen re-exposure. However, recent advances in monitoring antigen-experienced B cells have revealed the considerable heterogeneity of memory B cells, which include unswitched IgM(+) and/or unmutated memory B cells. The IgM and IgG type memory B cells reside in distinct locations and appear to possess distinct origins and effector functions, together orchestrating humoral memory responses.
"The mIg and the Igα/Igβ heterodimer are associated through non-covalent interactions5,6. Primary Ab responses are the results of the activation of mature naïve B cells, while memory or secondary Ab responses result from the activation of memory B cells2,7. The mIg subunits of BCRs expressed by mature naïve B cells and most memory B cells are different. "
[Show abstract][Hide abstract] ABSTRACT: Acquired immunological memory is a striking phenomenon. A lethal epidemic sweeps through a naïve population, many die but those who survive are never "attacked twice - never at least fatally", as the historian Thucydides observed in 430 BCE. Antibody memory is critical for protection against many human infectious diseases and is the basis for nearly all current human vaccines. Antibody memory is encoded, in part, in isotype-switched immunoglobulin (Ig)G-expressing memory B cells that are generated in the primary response to antigen and give rise to rapid, high-affinity and high-titered antibody responses upon challenge with the same antigen. How IgG-B-cell receptors (BCRs) and antigen-induced IgG-BCR signaling contribute to memory antibody responses are not fully understood. In this review, we summarize exciting new advances that are revealing the cellular and molecular mechanisms at play in antibody memory and discuss how studies using different experimental approaches will help elucidate the complex phenomenon of B-cell memory.Cell Research advance online publication 20 May 2014; doi:10.1038/cr.2014.65.
Cell Research 05/2014; 24(6). DOI:10.1038/cr.2014.65 · 12.41 Impact Factor
"The findings of toxin A488+ve CD19-positive/IgD-negative and CD19-positive/IgD-positive cells are consistent with the presence of switched (IgD-negative) and unswitched (IgD-positive), toxin A-specific memory B cells. They also reflect heterogeneity in the generation of memory B cell populations . However, the functional contributions of these distinct subpopulations of cells in host protection remains to be determined. "
[Show abstract][Hide abstract] ABSTRACT: C. difficile infection (CDI) is rarely reported in cystic fibrosis (CF) patients despite frequent hospitalisations and antibiotic usage. Conversely, the prevalence of CDI in inflammatory bowel disease (IBD) has received increased attention. We investigated components of the IgG-specific humoral immune response to C. difficile toxins A and B in patients with C. difficile-associated diarrhoea (CDAD), IBD patients with CDI, CF patients and healthy controls. Serum anti-toxin IgG was determined by ELISA. Circulating antigen-activated B-cells were investigated using Alexa Fluor 488-labelled toxin A and assessed by flow cytometry. Following induction of differentiation of memory B-cells, toxin A- and B-specific antibody secreting cells (ASCs) were quantified using ELISpot. We present the first data showing levels of serum anti-toxin A and B antibodies were significantly higher in patients with CF (without a history of CDI) than in CDAD patients and were stably maintained over time. Notably, the CDAD patients were significantly older than the CF patients. We also show that circulating toxin A-specific memory B-cells (IgD-negative) can be detected in CDAD patients [0.92 (0.09-1.78)%], and were prominent (5.64%, 1.14%) in two CF patients who were asymptomatic carriers of C. difficile. There was correlation between toxin A- and B-specific ASCs, with significantly higher proportions of the latter seen. In some with CDAD, high serum antibody levels were seen to only one of the two toxins. Mucosal secretion of toxin-specific IgG was detected in an additional group of IBD patients with no history of CDI. We conclude that enhanced and stable humoral immune responses to toxins A and B may protect CF and some IBD patients against CDI. The impaired ability to generate strong and/or sustained toxin-specific antibody and memory B-cell responses may increase susceptibility of older patients to CDI and highlight the need to investigate the role of immune senescence in future studies.
PLoS ONE 09/2013; 8(9):e74452. DOI:10.1371/journal.pone.0074452 · 3.23 Impact Factor
"In man these cells are thought to be the circulating equivalent of the marginal zone B cells of the spleen, which are of the IgM isotype but show evidence of somatic hypermutation in their immunoglobulin genes and protect against S. pneumoniae . Their origins and function remain a matter of considerable debate  . A reliance on splenic marginal zone cells would help explain the poor response to pure polysaccharide vaccine in the very young, since this B cell compartment is not fully formed in humans until 2 years of age . "
[Show abstract][Hide abstract] ABSTRACT: Vaccinations are powerful tools to help prevent/minimize the consequences of infections. Currently available vaccines are protecting only part of the human population because of the age-related decrease in immune functions. Vac-cination against Streptococcus pneumoniae and influenza are strongly recommended in children under 2 years of age and individuals over 65 years of age to protect them from infection. However, although commercially available vaccines against these infectious diseases provide protection and ensure lasting immunological memory in children and adults, they are much less effective in elderly individuals. The mechanisms for the reduced response of the elderly to pneumococcal and influenza vaccines are discussed in this review from the perspective of deficiencies seen in B cell function with age.
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