"Little Girl in the Big Ten" is the twentieth episode of Season 13.
In order to avoid a failing grade in gym, Lisa takes up gymnastics, which she uses to pose as a college student. Meanwhile, Bart is diagnosed with "Panda" virus and is forced to spend a week living in a plastic bubble.
Lisa is having trouble in gym and, to avoid failing, Mrs. Pommelhorse suggests that she enroll in a private gymnastics class taught by Coach Lugash. At first, Lisa feels it is pointless, but after falling and hitting her head, she is visited in a dream by John F. Kennedy, who tells her that athletics are just as important as academics. Lisa chooses to enroll in the class, and proves to be really good at gymnastics, which Lugash credits to her having a large head that gives her perfect balance. After class, she meets Tina and Carrie, two girls who happen to very similar to her. Lisa quickly realizes that they are actually college students; they explain that because of their "small gymnast bodies", they are often mistaken to be much younger than they actually are. Lisa lies to them by saying that she is a college student as well, as she wants to earn their friendship. They give her a ride home in their car and invite her to one of Robert Pinsky's poetry readings.
Meanwhile at Krusty Burger, Bart is bitten by a Chinese mosquito and becomes infected with the Panda Virus. To prevent it from being caught by other people, Dr. Hibbert places him inside a giant plastic bubble. Bart has trouble adapting to life inside the bubble due to problems such as not being able to eat and take a bath, although Homer fills the bubble with water and rolls it around the yard to give him a "bath".
Lisa thinks she is getting away with pretending to be a college student because she is going to poetry readings at night and then attending her second grade class at school in the day. While she goes to Springfield University, Milhouse, Martin and Database follow her. While Lisa is at a lecture about Itchy and Scratchy (specifically, the episode Butter Off Dead), they blow Lisa's cover and her college friends decide that they don't like her anymore. Lisa also loses her friends that are her own age because she went off with college kids.
Bart gets used to his bubble and uses it to become popular while also amusing Homer. Bart tells Lisa that in order to get her friends back, she has to pull a prank on Principal Skinner. The next day, while Superintendent Chalmers is dedicating a parking annex to Skinner for his years of service as "interim principal", Bart rolls Lisa while she is inside his bubble. He then pushes her off the school roof, and she lands on the chocolate cake next to Principal Skinner. The chocolate cake splatters all over Principal Skinner. Lisa then gets her old friends back because of this, and Bart develops agorophobia after being outside his bubble and goes to live in an air vent, only to get sucked down.