Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI1403310.15789/2220-7619-EOB-14033REVIEWSОБЗОРЫReview ArticleInteraction of b-cell receptors and antigens with different spatial arrangementВзаимодействие в-клеточных рецепторов и антигенов с различным пространственным расположениемhttps://orcid.org/0000-0003-1993-062285471697005958-4703TalayevVladimir Yu.ТалаевВладимир Юрьевич
Russian Federation

DSc (Medicine), Professor, Head of the Laboratory of Cellular Immunology

д.м.н., профессор, зав. лабораторией клеточной иммунологии

talaev@inbox.ruhttps://orcid.org/0000-0003-4097-6780364711394008340-7583SvetlovaMaria V.СветловаМария Владимировна
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Cellular Immunology

к.б.н., старший научный сотрудник лаборатории клеточной иммунологии

marya.talaeva@yandex.ruhttps://orcid.org/0000-0001-5063-311185471698003522-4289ZaichenkoIrina Ye.ЗаиченкоИрина Евгеньевна
Russian Federation

PhD (Biology), Leading Researcher, Laboratory of Cellular Immunology

к.б.н., ведущий научный сотрудник лаборатории клеточной иммунологии

imm.irina@mail.ruhttps://orcid.org/0000-0003-4527-61348547169900BabaykinaOlga N.БабайкинаОльга Николаевна
Russian Federation

PhD (Medicine), Senior Researcher, Laboratory of Cellular Immunology

к.м.н., старший научный сотрудник лаборатории клеточной иммунологии

olga_babaykina@inbox.ruhttps://orcid.org/0000-0003-1801-9693568413167006615-7674VoroninaElena V.ВоронинаЕлена Викторовна
Russian Federation

PhD (Biology), Senior Researcher, Laboratory of Cellular Immunology

к.б.н., старший научный сотрудник лаборатории клеточной иммунологии

el2v@mail.ru2214-7677ChistyakovSergey I.ЧистяковСергей Иванович
Russian Federation

DSc (Medicine), Professor, Chief Physician

д.м.н., профессор, главный врач

nock4328880@mail.ruAcademician I.N. Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology of Federal Service for Surveillance on Consumer Rights Protection and Human WellbeingФБУН Нижегородский научно-исследовательский институт эпидемиологии и микробиологии им. академика И.Н. Блохиной РоспотребнадзораN.Ya. Klimova Nizhny Novgorod Regional Blood CenterГБУЗ НО Нижегородский областной центр крови им. Н.Я. Климовой08112023301120231358098212806202328082023Copyright ©; 2023, Talayev V.Y., Svetlova M.V., Zaichenko I.Y., Babaykina O.N., Voronina E.V., Chistyakov S.I.Copyright ©; 2023, Талаев В.Ю., Светлова М.В., Заиченко И.Е., Бабайкина О.Н., Воронина Е.В., Чистяков С.И.2023Talayev V.Y., Svetlova M.V., Zaichenko I.Y., Babaykina O.N., Voronina E.V., Chistyakov S.I.Талаев В.Ю., Светлова М.В., Заиченко И.Е., Бабайкина О.Н., Воронина Е.В., Чистяков С.И.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/14033

B-cell receptors can interact with antigen epitopes on various objects: macromolecules, microorganisms or on the surface of other cells, e.g., follicular dendritic cells. Accordingly, B cells, on the one hand, have the ability to evaluate the location of pathogen surface epitopes, and, on the other hand, they must adapt their receptor apparatus to different epitope locations and antigen-bearing surface properties. Indeed, B-cell receptors and antibodies better bind objects with regular and dense epitope arrangement characteristic of many pathogens. As a result, such epitope arrangement can be recognized as a pathogen-associated geometric pattern, but the conditions for such recognition depend on the isotype of membrane immunoglobulin and the degree of B cell maturity. Young B cells express membrane IgM, which is involved in B cell development and the selection of their repertoire. Receptors with IgM do not impose strict requirements on epitope location and can activate B cells even upon binding a monovalent antigen. Receptors with membrane IgD are expressed later and predominate on naive B cells before entering the immune response. These receptors are optimized for two-point antigen binding and strictly require this type of interaction to induce an activation signal. Before contact with antigen, B-cell receptors are grouped in discrete membrane zones — nanoclusters, due to close interactions with the actin cytoskeleton. Contact with the antigen leads to the detachment of receptors from the cytoskeleton, rise in their mobility and the combining nanoclusters into microclusters — large clusters enriched with signaling molecules. The most dynamic changes are observed upon contact with an antigen fixed on the membrane of adjacent cell. In this case, free actin moves to the periphery of the intercellular contact zone, where it forms the cytoskeleton of the processes carrying receptor clusters. The processes spread across the surface of the partner cell and then contract, moving the antigen-binding microclusters to the center of the contact zone. Finally, the microclusters combine into a central cluster of the immune synapse, the intensity of the activation signal drops, and the cell prepares for endocytosis of antigens grouped at the local site. Thus, the structure of B-cell receptors can contribute to the response of the B-lymphocyte to antigens with a characteristic spatial location, while the dynamic interaction between B-cell receptor apparatus and the cytoskeleton allows optimizing the binding of antigens presented on various carriers. Knowledge on spatial aspects of antigen recognition may be useful for the construction of vaccines based on virus-like particles or antigens on other artificial carriers.

В-клеточные рецепторы могут взаимодействовать с эпитопами антигенов на различных объектах: макромолекулах, микроорганизмах или на поверхности других клеток, например, фолликулярных дендритных клеток. Соответственно, В-клетки, с одной стороны, имеют возможность оценивать расположение эпитопов на поверхности патогена, а с другой стороны, они должны адаптировать свой рецепторный аппарат к различным вариантам расположения эпитопов и свойствам несущих антиген поверхностей. Действительно, В-клеточные рецепторы и антитела лучше связывают объекты с регулярным и плотным расположением эпитопов, характерным для многих патогенов. В результате, такое расположение эпитопов может распознаваться как патоген-ассоциированный геометрический паттерн, однако условия этого распознавания зависят от изотипа мембранного иммуноглобулина и степени зрелости В-лимфоцита. Юные В-клетки экспрессируют мембранный IgM, который участвует в развитии В-клеток и селекции их репертуара. Рецепторы с IgM не предъявляют жестких требований к расположению эпитопов и могут активировать В-клетку даже при связывании моновалентного антигена. Рецепторы с мембранным IgD экспрессируются позднее и преобладают на наивных В-клетках перед их вступлением в иммунный ответ. Эти рецепторы оптимизированы для двухточечного связывания антигена и строго нуждаются в таком типе взаимодействия для индукции активационного сигнала. До контакта с антигеном В-клеточные рецепторы сгруппированы в дискретных зонах мембраны — нанокластерах, за счет тесных взаимодействий с актиновым цитоскелетом. Контакт с антигеном ведет к отсоединению рецепторов от цитоскелета, росту их подвижности и объединению нанокластеров в микрокластеры — крупные скопления, обогащенные сигнальными молекулами. Наиболее динамичные изменения наблюдаются при контакте с антигеном, фиксированным на мембране другой клетки. В этом случае свободный актин перемещается на периферию зоны межклеточного контакта, где формирует цитоскелет отростков, несущих скопления рецепторов. Отростки распространяются по поверхности клетки-партнера, а затем сокращаются, перемещая связавшие антиген микрокластеры в центр зоны контакта. Наконец, микрокластеры объединяются в центральный кластер иммунного синапса, интенсивность активационного сигнала падает, и клетка готовится к эндоцитозу сгруппированных на локальном участке антигенов. Таким образом, структура В-клеточных рецепторов может способствовать реакции В-лимфоцита на антигены с характерным пространственным расположением, тогда как динамическое взаимодействие В-клеточного рецепторного аппарата с цитоскелетом позволяет оптимизировать связывание антигенов, представленных на разнообразных носителях. Знание пространственных аспектов распознавания антигенов может быть полезно для конструирования вакцин на основе вирусоподобных частиц или антигенов на других искусственных носителях.

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