Inclusion Criteria:

- Histologic proof of recurring or residual follicular B-cell non-Hodgkin's lymphoma
(grade I or II), by Revised European American Lymphoma Classification (REAL) or World
Health Organization (WHO) classifications which has relapsed or persisted after 3 or
fewer conventional therapies, including chemotherapy or monoclonal antibody therapy;
note: all patients with previously treated B-cell lymphomas of any histology with the
exception of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) are
eligible

- Tumor measurable by computed tomography (CT) scans (at least one pathologic node
measuring 2.0 x 2.0 cm, or 2 nodes measuring > 1.5 x 1.5 cm after collection of tumor
for immunologic analyses)

- At least one prior treatment regimen but no more than 3 prior chemotherapy regimens;
patients previously treated with monoclonal antibodies or radiotherapy to a single
site will be eligible; these therapies will be considered prior treatment regimens
but will not be considered as prior chemotherapy; tumor vaccines will not be counted
as prior therapies, as all such agents are investigational

- Absolute neutrophil count (ANC) >= 1000/uL

- Platelets (PLT) >= 75,000/uL

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) =< 3 x upper limit or normal (ULN)

- Creatinine =< 1.5 x ULN

- Hemoglobin >= 8 g/dL

- Ability to provide informed consent

- Willingness to return to the Mayo Clinic Rochester or the University of California,
Los Angeles for follow up

- Life expectancy >= 24 weeks

- Willingness to provide all biologic specimens as required by the protocol

Exclusion Criteria:

- Known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4

- Any uncontrolled infection, hepatitis C virus (HCV)+ (unless HCV ribonucleic acid
[RNA]-negative by polymerase chain reaction [PCR]) or hepatitis B surface antigen
(HBsAg)+, or human immunodeficiency virus (HIV) positive patients or patients with
known immune deficiency states

- Previous MDX-010 therapy regardless of interval since last treatment

- Prior treatment with fludarabine or 2-chlorodeoxyadenosine =< 12 months prior to
registration

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- New York Heart Association classification III or IV or a history of angina pectoris
requiring active treatment

- Clinical evidence of central nervous system involvement by lymphoma

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragm, birth control pills, injections, intrauterine
device [IUD], or abstinence, etc.)

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)

- Diagnosis of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL)

- Any requirement for concurrent steroid therapy, including use of inhaled steroids for
asthma

- History of autoimmune disease requiring systemic therapy with immunosuppressive
drugs, including but not limited to rheumatoid arthritis, inflammatory bowel disease,
systemic lupus erythematosus, multiple sclerosis, or psoriasis

- Antinuclear antibody (ANA) titer or rheumatoid factor titer > 3x institutional ULN