The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

Mamani-Matsuda, Maria; Cosma, Antonio; Weller, Sandra; Faili, Ahmad; Staib, Caroline; Garçon, Loïc; Hermine, Olivier; Beyne‐Rauzy, Odile; Fieschi, Claire; Pers, Jacques‐Olivier; Arakelyan, Nina; Varet, Bruno; Sauvanet, Alain; Berger, Anne; Paye, François; Andrieu, Jean‐Marie; Michel, Marc; Godeau, Bertrand; Buffet, Pierre; Reynaud, Claude‐Agnès; Weill, Jean‐Claude

doi:10.1182/blood-2007-11-123844

Cited by 156 publications

(146 citation statements)

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“…First, the kinetics, magnitude, and affinity of the TI and TD responses were quite similar. Both responses exhibited a relatively short primary phase versus a prolonged secondary and both maintained the high affinity achieved late in the primary (by week 16), even as the titers began to wane (week [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. This heightened affinity continued into the secondary, with even a slight increase (∼from −log aK 5.9 to 6.2), late in the secondary.…”

Section: Discussionmentioning

confidence: 99%

“…bone marrow versus anterior kidney). One unexplored facet, however, has been the observation that the two distinct cellular arms of mammalian memory, the MBCs and LLPCs, possess distinctly different regionalities, with MBCs centered in peripheral tissues [35][36][37], and LLPCs within the primary lymphoid tissues [29][30][31]. As teleosts possess neither bone marrow nor lymph nodes, the question arises whether comparable regional patterns of dissemination occur in the teleost as well and, if so, whether distinct functional differences are imparted to these different organizational divisions.…”

Section: Introductionmentioning

confidence: 99%

“…The spleen; however, may play a slightly more dominant role, on a per cell basis, during the primary response. This distribution also mirrors the mammalian MBC distribution, wherein MBCs preferentially reside in the periphery as opposed to central lymphoid tissues [35][36][37].The differentiative potential of antigen-inducible cells (including MBCs) derived from the blood, spleen and anterior kidney was explored via HU pulsing in the presence or absence of antigen (Fig. 5).…”

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confidence: 99%

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Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

Kaattari

2013

Eur J Immunol

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The disposition of teleost memory and plasma cells (PCs) has essentially been unexplored. As the organization of the teleost immune system differs significantly from that of mammals (i.e. no bone marrow or lymph nodes, hematopoietic anterior kidney), this disposition could be essential in understanding how comparable functions are achieved. To address this question, the primary and secondary antibody-secreting cell, B memory cell, and antibody responses to T-independent and T-dependent antigens were analyzed in trout. Although the TI and TD antibody responses did not differ substantively from one another, the secondary responses to both were significantly prolonged compared with the primary responses. Logarithmic increases in titer and affinity were achieved for both antigens during the primary, with only modest increases during the secondary response. Antibody-secreting cells, both PCs and plasmablasts, quantitatively paralleled antibody production, with antibody-secreting cells skewing to the hematopoietic anterior kidney for both antigens. However, the enhanced antigen-inducible response of immune fish (indicative of the memory pool) skewed to the peripheral blood and spleen. This pattern of memory versus PC disposition parallels that observed in mammals even though the organization of the respective immune systems differs considerably. Keywords: Anterior kidney r Memory cells r Plasma cells r Trout IntroductionTeleost memory has been defined by the development of a differentially heightened responsive state to antigen, albeit lacking in a number of mammalian features. Primary immunization can, thus, lead to increased immunogen sensitivity [1], enhanced in vivo [2][3][4][5][6] and in vitro [6][7][8] antibody responsiveness, expansion of antigen-sensitive precursor pools [9] and, most importantly, anamestic responses to pathogens [4,5,10,11] and immunoprophylaxis [4,[12][13][14]. Anamestic features absent from teleost responses include isotype switching [15] (although they possess multiple isotypes [16]), relatively modest somatic mutaCorrespondence: Dr. Stephen L. Kaattari e-mail: kaattari@vims.edu tion [17][18][19] and affinity maturation [20][21][22] as compared with the IgG responses of mammals. Intriguingly, characteristics of teleost memory B cells (MBCs) [9] parallel those associated with a class of mammalian MBCs. Recent evidence reveals that human MBCs can include unswitched, mutated IgM + cells [23]; nonmutated, CD27 + IgM + cells [24], those induced by T-independent (TI) antigens [25,26], preimmune diversified repertoires [27] (as has recently been posed for the catfish [19]), or arise independently of GCs [27,28]. Together, these previous studies prompt a renewed focus on the critical elements of μ specific memory, both in teleosts and mammals. For example, perhaps the requisites for exceptionally high-titered, extensively mutated, high-affinity responses in * These authors contributed equally to this work. [32][33][34], which home to their respective hematopoietic tissues, even though the organs ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

Kaattari

2013

Eur J Immunol

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“…Identifying the magnitude and tissue distribution of specific memory T and B cells could be another critical component for assessments of vaccine efficacy with regard to a long-term protective effect [16]. For humoral immunity, it is well known that long-lived plasma cells, but not memory B cells, reside in the bone marrow (BM), while memory B cells are primarily located in the spleen in both mice and humans [17][18][19]. Recent discoveries have demonstrated that the BM is a site where memory CD4 + T cells reside, while the exact location of memory CD8 + T cells is still insufficiently known [20].…”

Section: "Only Very Few Adjuvants Have Been Approved Formentioning

confidence: 99%

Is the choice of vaccine adjuvant critical for long-term memory development?

Lycke¹

2010

Expert Review of Vaccines

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“…Despite the therapeutic efficacy of rituximab and methotrexate combinations, the majority of responding patients evidence only a 20% improvement in disease severity (American College of Rheumatology 20) (1)(2)(3)(4). Because rituximab results in near-complete and longlasting B cell depletion, both in the periphery and in secondary lymphoid organs (5,6), efforts to improve outcomes by increasing potency are likely to meet with limited success (4). Furthermore, the discordance between the ability of rituximab to mediate rapid B cell depletion in vivo (7,8) (hours to days) and the delay in maximal treatment effect (weeks to months) implies that downstream effects of B cell loss likely contribute to clinical improvement (9).…”

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confidence: 99%

Anti-CD20 Antibody with Multimerized Fc Domains: A Novel Strategy To Deplete B Cells and Augment Treatment of Autoimmune Disease

Zhang

Olsen

Chen

et al. 2016

The Journal of Immunology

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We developed a fully recombinant anti-CD20 protein derived from cDNA encoding one Fab domain, two IgG1 Fc regions, the IgG2 hinge, and an isoleucine zipper. This protein, called GB4542, contained both the homodimer and higher-order multimers. Binding studies revealed that GB4542 preferentially bound CD20+ cells yet also recognized CD20−FcγR+ PBMC. In contrast, a control mAb containing the identical Fab region, GB4500, failed to bind CD20−FcγR+ PBMC. Consistent with these findings, interactions between GB4542 and the canonical FcγRs had substantially lower KD values than correlate interfaces between GB4500 and these receptors. At low concentrations, GB4542 showed enhanced Ab-dependent cellular cytotoxicity, Ab-dependent cellular phagocytosis, and complement-dependent cytotoxicity compared with GB4500. However, at higher concentrations, an Fc analog of GB4542 inhibited anti-CD20 mAb–mediated B cell clearance through direct blocking of both Fc–FcγR interactions and C1q deposition on target cells. Furthermore, the higher-order multimer fraction of GB4542 demonstrated greater binding avidity with the canonical FcγRs and was associated with inhibitory effects observed in Ab-dependent cellular phagocytosis and complement-dependent cytotoxicity assays. These data suggest that GB4542 might have utility in the treatment of autoimmune diseases by combining both mAb-mediated B cell depletion and multimerized Fc-mediated tolerogenic effects.

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The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

Cited by 156 publications

References 31 publications

Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

Is the choice of vaccine adjuvant critical for long-term memory development?

Anti-CD20 Antibody with Multimerized Fc Domains: A Novel Strategy To Deplete B Cells and Augment Treatment of Autoimmune Disease

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