# FUNCTION OF THE B7 ANTIGEN ON NORMAL/NEOPLASTIC B CELLS

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1992 · $225,550

## Abstract

Human B cell activation antigens (ActAgs) are important cell surface
structures since they are candidates for receptors for growth and
differentiation factors, molecules involved in cell-cell interactions, or
molecules involved in microenvirommental localization.  In an attempt to
identify functionally important molecules, we developed mAbs against
several novel B cell activation antigens (ActAgs) and delineated their
expression on activated normal and neoplastic B cells.  One of these
ActAgs, termed B7, is a 5OkD glycoprotein member of the Ig superfamily
and is expressed on activated B cells, interferon-gamma treated
monocytes, and a subset of human B cell malignancies.  It is now known
that B7 is the ligand for the T cell restricted Ag CD28.  Ligation of
CD28 with either anti-CD28 mAb or our recombinant B7 induces a key
pathway of T cell activation resulting in augmented lymphokine secretion.
We believe that this newly described receptor ligand pair may important
for two reasons.  First, T cells activated through their T cell. receptor
complex require a co-stimulatory signal provided by B or other Ag
presenting cells to produce lymphokines, and if not received, become
tolerant.  Second, B cells require a cell-cell cognate interaction
delivered by the surface of activated T cells in order to exit G-O and
progress through G1.  Interaction of B7 with CD28 may mediate both of
these events.  We therefore postulate that B7 may be important in: 1)
inducing Ag specific class II restricted T cell activation, and 2)
interacting with the T cell surface molecule that regulates B cell G1
cycle entry, proliferation, and/or differentiation.  Our objective is to
determine the function of the B7 Ag on normal and neoplastic B cells.  In
this proposal, we plan: 1) To determine which T cell populations are
capable of binding B7 and to assess the functional consequences of
binding; 2) To determine whether CD28 or other T cell surface molecules
induce normal and neoplastic B cells to enter the cell cycle; and 3) To
determine whether B7 has a functional role in regulating the
proliferation. and/or differentiation of normal and neoplastic B cells.
These studies should permit us to determine the importance of the CD28:B7
receptor ligand pair in regulating T and B cell activation.  Moreover,
these studies may prove to be very clinically significant to our
understanding B cell diseases as well as in developing novel therapeutic
strategies.  B7+ B cell tumors may be regulated by CD28+ T cell derived
lymphokines in their microenvironment, or alternatively, CD28+ T cells
may directly induce Go neoplastic B cells to enter the cell cycle.
Similarly, uncontrolled expression of B7 by B cells may be associated
with polyclonal B cell activation, and therefore, potentially autoimmune
disease. Finally, and most importantly, inhibition of the B7:CD28 pathway
may be a strategy to induce specific T cell tolerance in the context of
organ transplantation.

## Key facts

- **NIH application ID:** 3179883
- **Project number:** 5R01CA040216-08
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** Lee Marshall Nadler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $225,550
- **Award type:** 5
- **Project period:** 1985-08-01 → 1995-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179883

## Citation

> US National Institutes of Health, RePORTER application 3179883, FUNCTION OF THE B7 ANTIGEN ON NORMAL/NEOPLASTIC B CELLS (5R01CA040216-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179883. Licensed CC0.

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