Гибридные клетки

Наши исследования, а также исследования других авторов показали, что существует еще один механизм активации онкогенов. Этот механизм действует при некоторых видах рака клеток иммунной системы, называемых В-клетками. Главная функция В- клеток заключается в образовании антител (иммуноглобулинов) — молекул, которые распознают антигены т.е. «не свои», чужеродные молекулы и связываются с ними. Для того чтобы В-клетка исправно выполняла свою функцию, экспрессия генов, которые кодируют антитела, должна быть значительной. В составе генов, которые обеспечивают синтез антител, имеются последовательности ДНК, усиливающие активность этих генов в В-клетках. Если при перестройке хромосом (палочкообразных структур, в которые организована ДНК клеточного ядра) в В-клетке такие последовательности окажутся рядом с онкогеном, экспрессия онкогена усилится и в функционировании этой клетки основное место займут процессы злокачественной трансформации.

Мы установили, что такие перестройки хромосом в В-клетках действительно происходят при лимфоме Беркитта — быстро развивающемся злокачественном заболевании иммунной системы. Перестройки заключаются в реципрокных транслокациях между двумя хромосомами В-клетки: от каждой из двух хромосом «отламывается» сегмент, который переносится на конец другой хромосомы (см. иллюстрацию на с. 20). В большинстве случаев в результате подобной транслокации онкоген оказывается вблизи последовательностей, усиливающих образование антител; реже онкоген остается на своем месте, а перемещается последовательность, усиливающая экспрессию.

Мы столкнулись с таким механизмом в ходе исследований, начатых в конце 1970-х годов с целью идентифицировать хромосомы, содержащие гены, ответственные за образование антител. Определив локализацию этих генов, мы обратили внимание на то, что они располагаются именно на тех хромосомах, которые, как уже было известно, подвержены транслокациям при лимфоме Беркитта. Дальнейшая работа показала, что два сегмента генетического материала, которыми обмениваются хромосомы, содержат соответственно онкоген и ген, кодирующий часть молекулы антитела.

ЧТОБЫ установить, какие хромосомы несут генетическую информацию, определяющую образование антител, один из авторов этой статьи — К. Кроче — и его сотрудники применили экспериментальный подход, основанный на гибридизации соматических клеток мыши и человека (соматическими называют неполовые клетки тела).

Гибридные клетки получают, смешивая В-клетки мыши и человека в среде, которая содержит фактор (химической или вирусной природы), вызывающий слияние клеток разных видов. Образующиеся клетки содержат хромосомы и мыши, и человека.



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