Different B Cell Populations Mediate Early and Late Memory During an Endogenous Immune Response

Pape, Kathryn A.; Taylor, Justin J.; Maul, Robert W.; Gearhart, Patricia J.; Jenkins, Marc K.

doi:10.1126/science.1201730

Cited by 498 publications

(716 citation statements)

References 26 publications

(34 reference statements)

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“…Given the functional heterogeneity of memory B-cell subsets (e.g., IgM + vs. IgG1 + memory B cells) (29,30), it is possible that each subset might differentially contribute to activation of T FH memory cells. Thus, better understanding of the regulatory mechanisms in the interactions of these memory B-cell subsets and T FH memory cells should provide important insights for development of better vaccines.…”

Section: Discussionmentioning

confidence: 99%

Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells

Ise

Inoue

McLachlan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (T FH ) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5 + T FH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with soluble antigen Bcl6 in memory T FH cells is rapidly induced in a dendritic cell-independent manner and that peptide:class II complexes (pMHC) on cognate memory B cells significantly contribute to this induction. Given the previous evidence that antigen-specific B cells residing in the follicles acquire antigens within minutes of injection, our results suggest that memory B cells present antigens to the cognate T FH memory cells, thereby contributing to rapid Bcl6 reexpression and differentiation of the T FH memory cells during humoral memory responses.immunological memory | antibody production T he development of high-affinity B-cell memory is essential in most effective vaccines that are in use today. Because most protein antigens require T-cell help to induce B-cell responses, understanding the mechanisms by which memory T and B cells are generated and maintained, as well as how their swift activation is executed, is of fundamental importance for vaccine development.In primary immune responses, it is widely accepted that among several differentiated helper T-cell subsets follicular helper CD4 T cells (T FH cells) are the major subset to deliver help to B cells (1). T FH cells express CXC-chemokine receptor 5 (CXCR5), the chemokine receptor for the B-cell homing chemokine CXCL13. Surface expression of CXCR5 enables T FH cells to migrate into B-cell follicles, where they provide help to B cells to form germinal centers. In addition, T FH cells are needed for the crucial affinitymaturation process of B cells in germinal centers, whereby Agspecific B cells undergo repeated rounds of somatic hypermutation and positive selection by T FH cells to rapidly evolve high-affinity somatically mutated B-cell receptors. B-cell lymphoma 6 (Bcl6) has recently been identified as a T FH lineage regulator (2-4); it is highly expressed by T FH cells and is required for their development. According to the current view, during a primary response Bcl6 expression by T cells is induced by priming with dendritic cells (5-7) and ICOS is a key coreceptor molecule for induction of Bcl6 (5, Although the importance of Bcl6 and its expression kinetics in naïve T-cell differentiation have been well elucidated, its role and activation mechanisms in T FH memory cells still remain obscure. Hence, in this paper we first focus upon the roles of Bcl6, demonstrating its importance for maintenance of T FH memory cells. Then, we show that Bcl6 in memory T FH cells was rapidly induced upon rechallenge with soluble antigen and that this response was mainly mediated through antigen presentation by the cognate memory B cells. Given the good association between Bcl6 wi...

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Section: Discussionmentioning

confidence: 99%

Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells

Ise

Inoue

McLachlan

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…We recently showed that MCMV induces poor CD8 T-cell response to challenges with emerging viral infections and that this poor response correlates to the frequency of the (Dogan et al, 2009;Pape et al, 2011;Tomayko et al, 2010). IgM memory B-cells persist long after the clearance of an infection, whereas the conventional memory cells are described as the frontline responders to infections (Good-Jacobson and Tarlinton, 2012).…”

Section: Effects Of Latent Infections On the Peripheral Memory B-cellmentioning

confidence: 99%

Mouse CMV infection delays antibody class switch upon an unrelated virus challenge

Marandu¹,

Finsterbusch²,

Kröger³

et al. 2014

Experimental Gerontology

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“…IgM+) memory cells (NSM; CD27+IgD+) [8]. During secondary antigen exposure SM B-cells proliferate rapidly and differentiate into antibody secreting cells, while NSM cells are able to reinitiate GC reaction and replenish SM fraction [9,10]. Because B-cell response to nuclear auto-antigens requires T-cell help, formation of pathogenic autoantibodies in SLE (e.g.…”

Section: Introductionmentioning

confidence: 99%

Changes of memory B- and T-cell subsets in lupus nephritis patients

Kosałka

Jakieła

Musiał

2015

Folia Histochem Cytobiol.

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Introduction. Renal involvement in systemic lupus erythematosus (SLE) is associated with production of antibodies to double stranded DNA, deposition of immune complexes and organ damage. These processes have been linked with abnormalities in B-and T-cell memory compartments. The aim of the study was to analyze subsets of peripheral memory B-cells and T-cells in lupus nephritis (LN) patients. Material and methods. We used multicolor flow cytometry to analyze major memory subsets of peripheral blood B-cells (defined by CD27, IgD and CD21) and T-cells (CD45RA, CD45RO, CCR7) in 32 patients with active or inactive LN, and 23 control subjects. Results. Lupus nephritis patients were characterized by increased percentage of immature/early-transitional B-cells (CD27-IgD+CD21-), higher frequency of activated switched memory (SM, CD27+IgD-CD21-) and exhausted memory B-cells (CD27-IgD-), and decrease in non-switched memory (NSM, CD27+IgD+) B-cells. CD21 low subsets (immature and activated B-cells) were particularly expanded in patients with active disease. In both groups of LN patients we observed decline in the absolute count of NSM B-cells. It was paralleled by lymphopenia in naïve CD4+ T-cell compartment and increase in the frequency of effector memory T-cells, and these changes were more pronounced in active LN. Conclusions. B-cell memory compartment in LN is deficient in NSM cells and during active disease it is further skewed towards SM and exhausted memory phenotypes, most likely as a cause of chronic antigenic stimulation. Parallel changes in T-helper cell subsets suggest a similar mechanism of SLE-related lymphopenia for both B-cell and T-cell compartment.

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Different B Cell Populations Mediate Early and Late Memory During an Endogenous Immune Response

Cited by 498 publications

References 26 publications

Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells

Memory B cells contribute to rapid Bcl6 expression by memory follicular helper T cells

Mouse CMV infection delays antibody class switch upon an unrelated virus challenge

Changes of memory B- and T-cell subsets in lupus nephritis patients

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