Тяжелые цепи

В 1979 г. Кроче и его сотрудники, анализируя гибридные клетки, обнаружили, что тяжелые цепи, характерные для иммуноглобулинов человека, могут синтезироваться только в тех клетках, которые содержат 14-ю хромосому человека. Используя ту же методику эксперимента Я. Эриксон, Дж. Мартинис и Кроче в 1981 г. установили, что 22-я хромосома кодирует легкие цепи с константным X- участком. В 1982 г. О. Уэсли МакБрайд и его коллеги в Национальном институте рака, а также Т. Рэббитс с сотрудниками в Лаборатории молекулярной биологии Совета медицинских исследований в Кембридже выяснили, что 2-я хромосома кодирует легкие цепи с константным х- участком.

ЗТИ результаты полностью согласовывались с исследованиями хромосомных транслокаций, которые были выполнены на 10 лет ранее. В 1972 г. Дж. Манолов и Я. Манолова, работавшие в то время в Швеции, в Лундском университете, обнаружили, что в хромосомах многих клеток, пораженных злокачественной лимфомой Беркитта, имеет место аномалия: одна из хромосом в 14-й паре (соматические клетки человека содержат 23 различные пары хромосом) гораздо длиннее, чем обычно. Поскольку ненормально длинным был участок хромосомы, называемый плечом q, Маноловы обозначили необычную хромосому 14<7+.

Впоследствии в Королевском институте (Стокгольм) Л. Зек в сотрудничестве с одним из авторов статьи — Дж. Клейном — показали, что хромосома 14<7+ образуется в результате реципрокной транслокации: от одной из хромосом 8-й пары отделяется сегмент и присоединяется к концу 14-й хромосомы. Перестроенная

8-я хромосома получила обозначение 8q~ , поскольку ее плечо q укорочено. Позже другие исследователи установили, что в клетках лимфомы Беркитта могут происходить хромосомные перестройки двух других типов, также затрагивающие 8-ю хромосому. Приблизительно в 16% случаев заболевания лимфомой Беркитта реципрокное перемещение сегментов происходит между 8-й и 22-й хромосомами и примерно в 9% случаев — между 2-й и 8-й хромосомами. Три из подверженных этим транслокациям хромосом — 2, 14 и 22-я — участвуют в образовании антител.

Вскоре выяснилось, что связь между лимфомой Беркитта и синтезом антител более тесная. Кроче и Эриксон в Вистаровском институте анатомии и биологии и Дж. Файнен и П. Ноуэлл в Медицинской школе Пенсильванского университета показали, что при транслокации на 8-ю хромосому точка разрыва 14-й хромосомы расположена как раз в том участке, который кодирует тяжелые цепи иммуноглобулинов.

 

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