Two waves of memory B-cell generation in the primary immune response

Inamine, Ayako; Takahashi, Yoshimasa; Baba, Nobue; Miyake, Kensuke; Tokuhisa, Takeshi; Takemori, Toshitada; Ryo, Akihide

doi:10.1093/intimm/dxh241

Cited by 93 publications

(92 citation statements)

References 51 publications

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“…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. Th is result is consistent with previous fi ndings that premature B mem cells can be produced in mice in which germinal centre formation is inhibited by anti-ICOS Ab administration 56 or Bcl-6 defi ciency 27 .…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2011

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In response to T cell-dependent antigens, B cells proliferate extensively to form germinal centres (GC), and then differentiate into memory B (B mem ) cells or long-lived plasma cells (LLPCs) by largely unknown mechanisms. Here we show a new culture system in which mouse na ï ve B cells undergo massive expansion and isotype switching, and generate GC-phenotype B (iGB) cells. The iGB cells expressing IgG1 or IgM / D, but not IgE, differentiate into B mem cells in vivo after adoptive transfer and can elicit rapid immune responses with the help of cognate T cells. Secondary culture with IL-21 maintains the proliferation of the iGB cells, while shifting their in vivo developmental fate from B mem cells to LLPCs, an outcome that can be reversed by withdrawal of IL-21 in tertiary cultures. Thus, this system enables in vitro manipulation of B-cell fate, into either B mem cells or LLPCs, and will facilitate dissection of GC-B cell differentiation programs.

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Section: Discussionsupporting

confidence: 92%

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

et al. 2011

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“…In particular DN B cells obtained from healthy elderly people, show a lower rate of somatic hypermutation (manuscript in preparation), so the reduction of the rate of mutation might be due to a total disconnected generation of these cells, in elderly, from either germinal centers or T cell help. In view of the lack of CD27 expression and the low rate of somatic mutation in IgG + CD27 − B cells, here shown and reported by others (Anolik et al, 2004;Fecteau et al, 2006), it has been hypothesized that IgG + CD27 − B cells might be a first wave of memory B cells (Blink et al, 2005;Inamine et al, 2005) or a pool of short-lived memory B cells (Dorner and Radbruch, 2005), in contrast to the IgG + CD27 + B cells that could be more related to long-lived memory B cells. Alternatively DN B cells might represent activated follicular cells that initiate germinal center reaction, after receiving early CD154-mediated T cell help, but fail to progress through this pathway.…”

Section: Discussionmentioning

confidence: 52%

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Bulati¹,

Buffa²,

Candore³

et al. 2011

Ageing Research Reviews

101

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a b s t r a c tImmunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG + IgD − CD27 − ) that we have demonstrated is increased in healthy elderly.

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“…B cells that acquire increased affinity for Ag preferentially survive within the GC and subsequently differentiate into long-lived PCs or memory B cells, both of which contribute to long-term immunity. Early memory B cells can also be generated independently of the GC response and, unlike early PBs and GC B cells, can migrate into the blood and to distal lymphoid tissues (7,8). Contrary to a commonly held belief, Ig class switch recombination is not restricted to the GC and can begin as early as 2 days after immunization with TD Ag (9,10).…”

Section: H Umoral Immune Responses Against Foreign T-dependent (Td)mentioning

confidence: 99%

Antigen Affinity Controls Rapid T-Dependent Antibody Production by Driving the Expansion Rather than the Differentiation or Extrafollicular Migration of Early Plasmablasts

Chan

Gatto²,

Wood³

et al. 2009

The Journal of Immunology

206

222

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To optimize the initial wave of Ab production against T-dependent Ags, primary B cell clones with the highest Ag affinity are selected to generate the largest extrafollicular plasmablast (PB) responses. The mechanism behind this remains undefined, primarily due to the difficulty of analyzing low frequency Ag-specific B cells during the earliest phases of the immune response when key differentiation decisions are made. In this study, a high resolution in vivo mouse model was used to characterize in detail the first 6 days of a T-dependent B cell response and to identify the steps at which initial Ag affinity has a major impact. Ag-specific B cells proliferated within splenic follicles from days 1.0 to 3.0 before undergoing a dynamic phase of multilineage differentiation (days 3.0–4.0) that generated switched and unswitched populations of germinal center B cells, early memory B cells, and extrafollicular PBs. PB differentiation was marked by synchronous up-regulation of CXCR4 and down-regulation of CXCR5 and the adoption of a unique BCRhigh phenotype by unswitched PBs. Differences in Ag affinity of >50-fold did not markedly affect the early stages of the response, including the differentiation and extrafollicular migration of PBs. However, high affinity PBs underwent significantly greater expansion within the splenic bridging channels and red pulp, due to both increased proliferation and decreased apoptosis. Extrafollicular PBs maintained class II MHC, but not IL-21R expression, and interacted directly with Ag-specific extrafollicular Th cells, suggesting that IL-21-independent T cell help may drive extrafollicular PB expansion in responses to foreign Ag.

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Two waves of memory B-cell generation in the primary immune response

Cited by 93 publications

References 51 publications

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

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

B cells and immunosenescence: A focus on IgG+IgD−CD27− (DN) B cells in aged humans

Antigen Affinity Controls Rapid T-Dependent Antibody Production by Driving the Expansion Rather than the Differentiation or Extrafollicular Migration of Early Plasmablasts

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