Biology subjects

Bessell, E.

Publications and source records attributed to Bessell, E..

4 recordsLinked to original sources

bioRxiv2026

Characterisation of Peripheral Blood B Cell Receptor Repertoire in Severe Eosinophilic Asthma and EGPA

BackgroundSevere eosinophilic asthma (SEA), eosinophilic granulomatosis with polyangiitis (EGPA) and nasal polyposis (NP) are immune-mediated diseases characterised by eosinophilic inflammation. However, there is also increasing interest in the potential pathological roles of autoantibodies in these diseases. Understanding their B cell receptor (BCR) repertoires may provide valuable insights into disease mechanisms, and potential role of B cells in their pathology. MethodsWe conducted BCR repertoire sequencing using peripheral blood from 43 patients, comprising SEA with nasal polyps (SEA+NP), SEA without nasal polyps (SEA-NP), and EGPA, along with 16 healthy controls (HCs). ResultsCompared to HCs, patients with EGPA exhibited increased relative proportions of IgA1, IgG1, IgG2, and IgG4 subclasses. Similarly, SEA-NP patients demonstrated significantly high proportion of IgG2 sequences. Notably, the IgG4 subclass was significantly elevated across all patient groups compared to HCs. Patients receiving anti-IL-5/5R biologic treatments showed increased relative proportions of IgA2 and IgG2 subclasses compared to untreated patients. Some variation across participant groups in mean somatic hypermutation and mutation frequency was evident. 1,508 clones shared across patients, but not healthy controls, were evident though the majority showed low clonal expansion. Nevertheless, a few shared clones did show either high prevalence across patients and/or higher clonal expansion. ConclusionChanges in BCR repertoires in SEA/EGPA are consistent with a pattern of a more mature B cell component in the periphery and with the T2 inflammatory response observed in SEA and EGPA. BCR clonotypes shared across patients were evident, however, whether such clonotypes are pathological in SEA/EGPA requires further investigation.

immunology↗

bioRxiv2023

B cell-stromal cell cross talk drives mesenteric lymph node eosinophilia during intestinal helminth infection

Eosinophils are involved in host protection against multicellular organisms including helminths and often participate in regulating long-lasting humoral responses. However, their recruitment to the gut-draining mesenteric lymph node (mLN), where they support the development of the adaptive immune response is still elusive. Here, we demonstrate the mechanism underlying the recruitment of eosinophils to the murine mLN post gastrointestinal helminth infection. We found that mLN eosinophils accumulated at immune interactive sites such as the interfollicular and paracortical regions in an IL-4R-dependent manner and was directly associated with the reduced availability of stromal derived eosinophil chemoattractants. Using multiplex imaging we confirmed that eosinophils associate within a stromal niche containing Lyve1+ lymphatic vessels, ER-TR7+Pdpn+ FRCs, and extrafollicular CD138+ plasma cells. Experiments utilising complete and mixed bone marrow chimeras demonstrated that mice lacking IL-4R expression or LT{beta} expression selectively on B cells had diminished eosinophilia and reduced extrafollicular plasma cell numbers within the mLN. When co-cultured with LT{beta}R activated FRCs, eosinophils gained an active phenotype with enhanced Il1rl1 (ST2) receptor expression. LT{beta}R ligation on FRCs resulted in enhanced IL-33 expression along with enrichment of distinct reactomes. Additionally, deletion of LT{beta}R in FRCs reduced the homing capability of eosinophils to the mLN, confirming the significance of lymphotoxin signalling in granulocyte recruitment. Overall, these results highlight the previously unknown role of B cell-stromal cell crosstalk in driving mLN eosinophilia and their potential role in regulating the quality and magnitude of the humoral immune response generated within the mLN.

immunology↗

bioRxiv2020

Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans

Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations.

immunology↗

bioRxiv2020

Establishment of a pig influenza challenge model for evaluation of monoclonal antibody delivery platforms

Monoclonal antibodies are a possible adjunct to vaccination and drugs in treatment of influenza virus infection. However questions remain whether small animal models accurately predict efficacy in humans. We have established the pig, a large natural host animal for influenza, with many physiological similarities to humans, as a robust model for testing monoclonal antibodies. We show that a strongly neutralizing monoclonal antibody (2-12C) against the hemagglutinin head administered prophylactically at 15 mg/kg reduced viral load and lung pathology after pandemic H1N1 influenza challenge. A lower dose of 1 mg/kg of 2-12C or a DNA plasmid encoded version of 2-12C, reduced pathology and viral load in the lungs, but not viral shedding in nasal swabs. We propose that the pig influenza model will be useful for testing candidate monoclonal antibodies and emerging delivery platforms prior to human trials.

immunology↗